Gencalq 100 mg Capsule

GENCALQ is indicated for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

GENCALQ is indicated for the treatment of patients with chronic lymphocytic leukaemia (CLL).

Treatment with GENCALQ should be initiated and supervised by a medical practitioner experienced in the use of anticancer therapies.

Posology

MCL

The recommended dose of GENCALQ for the treatment of MCL is 100 mg (1 capsule) twice a day.

CLL

The recommended dose of GENCALQ for the treatment of MCL is 100 mg (1 capsule) twice a day, either as monotherapy or in combination with Obinutuzumab. Refer to the Obinutuzumab prescribing information for recommended Obinutuzumab dosing information. Doses should be separated by approximately 12 hours.

Treatment with GENCALQ should continue until disease progression or unacceptable toxicity.

Missed Dose

If a patient misses a dose of GENCALQ by more than 3 hours, instruct the patient to take the next dose at its regularly scheduled time. Extra capsules of GENCALQ should not be taken to make up for a missed dose.

Dose Adjustment

Recommended dose modifications of GENCALQ for Grade u2265 3 adverse reactions are provided in Table 1.

GENCALQ is contraindicated for the following:

• Hypersensitivity to acalabrutinib or any of the excipients listed in section 6.1.

Haemorrhagic events

Serious haemorrhagic events, including fatal events, have been reported in patients with haematologic malignancies (n=1040) treated with acalabrutinib monotherapy. The mechanism for the bleeding events is not well understood. Patients receiving antithrombotic medicines may be at increased risk of haemorrhage. Use caution with antithrombotic medicines and consider additional monitoring for signs of bleeding when concomitant use is medically necessary. Consider the benefit-risk of withholding GENCALQ for at least 3 days pre- and post-surgery.

Infections

Serious infections (bacterial, viral or fungal), including fatal events have been reported in patients with haematologic malignancies (n=1040) treated with acalabrutinib monotherapy. Grade 3 or higher infections occurred in these patients. The most frequently reported Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation, aspergillosis, and progressive multifocal leukoencephalopathy (PML) have occurred. Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat as medically appropriate.

Cytopeniau2019s

Treatment-emergent Grade 3 or 4 cytopeniau2019s, including neutropenia, anaemia and thrombocytopenia based on laboratory measurements, has been reported in patients with haematologic malignancies (n=1040) treated with acalabrutinib monotherapy. Monitor complete blood counts as medically appropriate.

Second Primary Malignancies

Second primary malignancies, including non-skin cancers have been reported in patients treated with acalabrutinib. The most frequent second primary malignancy reported is skin cancer. Skin cancers should be monitored.

Atrial Fibrillation and Flutter

In patients with haematologic malignancies (n=1040) treated with acalabrutinib monotherapy, Grade 3 atrial fibrillation/flutter have been reported in 1% of patients, and Grade 1 or 2 in 3% of patients. Monitor for symptoms (e.g., palpitations, dizziness, syncope, chest pain, dyspnoea) of atrial fibrillation and atrial flutter and obtain an ECG as appropriate.

GENCALQ contains sodium starch glycolate. GENCALQ contains less than 1 mmol sodium (23 mg) per dose, essentially 'sodium-free'.

Active substances that may increase acalabrutinib plasma concentrations

CYP3A Inhibitors

Co-administration of acalabrutinib with a strong CYP3A inhibitor (itraconazole) increases acalabrutinib plasma concentrations, which may result in increased toxicity. Consider alternative therapies that do not strongly inhibit CYP3A activity. Patients taking strong CYP3A inhibitors (e.g., ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, ritonavir, telaprevir, posaconazole, voriconazole) with GENCALQ should be monitored more closely for adverse reactions.

Active substances that may decrease acalabrutinib plasma concentrations

CYP3A Inducers

Co-administration of acalabrutinib with a strong CYP3A inducer (rifampin) decreases acalabrutinib plasma concentrations, which may result in reduced GENCALQ activity. Consider alternative therapies to strong inducers of CYP3A activity (e.g., phenytoin, rifampin, carbamazepine). Avoid St. Johnu2019s wort which may unpredictably decrease acalabrutinib plasma concentrations. If a strong CYP3A inducer cannot be avoided, increase the GENCALQ dose to 200 mg twice daily.

Gastric Acid Reducing medicines

Acalabrutinib solubility decreases with increasing pH. Co-administration with a proton pump inhibitor (40 mg omeprazole for 5 days), decreased acalabrutinib AUC by 43%. If treatment with an acid reducing medicine is required, consider using an antacid (e.g., calcium carbonate), or an H2-receptor antagonist (e.g., ranitidine or famotidine). For use with antacids, separate dosing by at least 2 hours. For H2-receptor antagonists, take GENCALQ 2 hours before taking the H2-receptor antagonist. Due to the long-lasting effect of proton pump inhibitors, separation of doses with proton pump inhibitors may not eliminate the interaction with GENCALQ.

Active substances whose plasma concentrations may be altered by GENCALQ

CYP3A Substrates

Based on in vitro data and PBPK modelling, no interaction with CYP substrates is expected at the clinically relevant concentrations (see section 5.2).

Effects of Acalabrutinib and its active metabolite, ACP-5862, on Drug Transport Systems

Acalabrutinib may increase exposure to co-administered BCRP substrates (e.g., methotrexate) by inhibition of intestinal BCRP (see section 5.2). ACP-5862 may increase exposure to co-administered MATE1 substrates (e.g., metformin) by inhibition of MATE1 (see section 5.2).

Women of childbearing potential

GENCALQ should not be used by women of childbearing potential, and they should be advised to avoid becoming pregnant while receiving GENCALQ.

Pregnancy

GENCALQ should not be used during pregnancy.

Breastfeeding

No data are available regarding the presence of acalabrutinib or its active metabolite in human milk. Breastfeeding mothers should not breastfeed during treatment with GENCALQ and for 2 days after receiving the last dose.

Fertility

There are no data on the effect of GENCALQ on human fertility.

GENCALQ has no or negligible influence on the ability to drive and use machines. However, during treatment with acalabrutinib, fatigue and dizziness have been reported and patients who experience these symptoms should be advised not to drive or use machines.

a) Summary of the safety profile

The most frequent reported adverse drug reactions of any grade in patients treated with acalabrutinib monotherapy, are infection, headache, diarrhoea, bruising, musculoskeletal pain, nausea, fatigue, and rash. The most frequently reported Grade u2265 3 adverse drug reactions are infection, neutropenia, and anaemia.

b) Tabulated list of adverse reactions

Tables 3 present the frequency category of adverse reactions observed in patients with Haematological malignancies treated with GENCALQ.

System Organ Class

All Grades

Grade u2265 3 Adverse Reactions /Frequency

Infections and infestations

Frequent

Infection

Frequent

Infection

Neoplasms benign, malignant, and unspecified (including cysts and polyps)

Frequent

Second primary malignancy

Non-melanoma skin cancer

Second primary malignancy excluding non-melanoma skin

Frequent

Second primary malignancy

Second primary malignancy excluding non-melanoma skin

Less Frequent

Non-melanoma skin cancer

Blood and lymphatic system disorders

Frequent

Leukopenia

Neutropenia

Anaemia

Thrombocytopenia

Frequent

Leukopenia

Neutropenia

Anaemia

Thrombocytopenia

Metabolism and nutrition disorders

Less Frequent

Tumour Lysis Syndrome

Less Frequent

Tumour Lysis Syndrome

Nervous system disorders

Frequent

Headache

Dizziness

Frequent

Headache

Less Frequent

Dizziness

Cardiac disorders

Frequent

Atrial fibrillation /Flutter

Frequent

Atrial fibrillation /Flutter

Vascular disorders

Frequent

Less Frequent

Haemorrhage/ Hematoma

Haemorrhage/ Hematoma

Respiratory, thoracic, and mediastinal disorders

Frequent

Epistaxis

Less Frequent

Epistaxis

Gastrointestinal disorders

Frequent

Diarrhoea

Nausea

Abdominal pain

Constipation

Vomiting

Frequent

Diarrhoea

Nausea

Abdominal pain

Less Frequent

Constipation

Vomiting

Skin and subcutaneous tissue disorders

Frequent

Bruising

Rash

Less Frequent

Rash

Musculoskeletal and connective tissue disorders

Frequent

Arthralgia

Musculoskeletal Pain

Frequent

Musculoskeletal Pain

Less Frequent

Arthralgia

General disorders and administration site conditions

Frequent

Fatigue

Asthenia

Frequent

Fatigue

Less Frequent

Asthenia

Investigations

Frequent

Decreased haemoglobin

Decreased platelets

Decreased absolute neutrophil count

Frequent

Decreased haemoglobin

Decreased platelets

Decreased absolute neutrophil count

Other special populations

Elderly

No clinically relevant differences in safety or efficacy observed between patients u2265 65 years and younger.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 or [email protected]

There is no specific treatment for GENCALQ overdose and symptoms of overdose have not been established. In the event of an overdose, patients must be closely monitored for signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.