Calquence Tablet, Film Coated Uses, Dosage & Side Effects

Grade 3 or greater non-hematologic toxicities,

Grade 3 thrombocytopenia with bleeding,

Grade 4 thrombocytopenia or

Grade 4 neutropenia lasting longer than 7 days

First and Second

Interrupt CALQUENCE.

Once toxicity has resolved to Grade 1 or baseline level, CALQUENCE may be resumed at 100 mg approximately every 12 hours.

Third

Interrupt CALQUENCE.

Once toxicity has resolved to Grade 1 or baseline level, CALQUENCE may be resumed at a reduced frequency of 100 mg once daily.

Fourth

Discontinue CALQUENCE.

Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

Adverse Reaction

Severity^a

Dosage Modification

(Starting dosage of CALQUENCE = 100 mg approximately every 12 hours)

Neutropenia^b [see Warnings and Precautions (5.3)]

Absolute neutrophil count less than 0.5 x 10⁹/L for greater than 7 days

Interrupt CALQUENCE. Once toxicity has resolved to Grade ≤ 2, resume CALQUENCE at starting dosage.

Upon 2nd or 3rd occurrence, reduce dosage of CALQUENCE to 100 mg once daily.^c

Discontinue CALQUENCE at 4th occurrence.

For bendamustine^b :

Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2, resume bendamustine and consider dosage reduction to 70 mg/m^2.d,e

Thrombocytopenia^f [see Warnings and Precautions (5.3)]

Platelet count 25 to 50 x 10⁹/L with clinically significant bleeding or platelet count less than 25 x 10⁹/L

Interrupt CALQUENCE. Once toxicity has resolved to Grade ≤ 2 or baseline, resume CALQUENCE at starting dosage.

If recurrence, reduce dosage of CALQUENCE to 100 mg once daily.^c

Consider discontinuing CALQUENCE at 3rd occurrence.

For bendamustinef:

Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2 or baseline, resume bendamustine and consider dose reduction to 70 mg/m^2.e

Non-hematologic adverse reactions [see Warnings and Precautions (5)]

Grade 3 or higher

Interrupt CALQUENCE. Once toxicity has resolved to Grade ≤ 2 or baseline, resume CALQUENCE at starting dosage.

If recurrence, reduce dosage of CALQUENCE to 100 mg once daily.^c

Discontinue CALQUENCE at 3rd occurrence of Grade 4 toxicity. For Grade 3 toxicity, consider the risks and benefits of continuing CALQUENCE.

For bendamustine:

Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2 or baseline, resume bendamustine and consider dose reduction to 70 mg/m^2.e

^a Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

^b For neutropenia with ANC less than 1 x 10⁹/L, consideration for bendamustine dose interruption and dosage reduction to 70 mg/m² may be appropriate in certain circumstances.

^c Dose may be re-escalated at the discretion of the physician if patient tolerates a reduced dose for ≥4 weeks.

^d Consider use of myeloid growth factors before bendamustine dosage reduction.

^e Consider discontinuing bendamustine if additional dosage reduction is required.

^f For thrombocytopenia, a platelet count below 50 x 10⁹/L should prompt bendamustine dose interruption even in the absence of clinically significant bleeding.

Adverse Reactiona

Adverse Reaction Occurrence

Dose Modification

Grade 3 or 4 neutropenia with or without fever and/or infection; Grade 4 neutropenia lasting more than 7 days

First occurrence

Interrupt CALQUENCE and/or venetoclax.b

Once toxicity resolves to Grade ≤ 1 or baseline, restart CALQUENCE and/or venetoclax at same dose.

Second occurrence

Interrupt CALQUENCE and/or venetoclax.b

Once toxicity resolves to Grade ≤ 1 or baseline, restart CALQUENCE at same dose and venetoclax at one lower dose levelc.

Subsequent occurrence

Withhold CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1 or baseline.b,d

Grade 3 or 4 thrombocytopenia and/or bleedingf

First occurrence

Interrupt CALQUENCE and/or venetoclax. When bleeding resolves and thrombocytopenia is Grade ≤ 1 or baseline without transfusion support for 5 consecutive days, restart CALQUENCE and/or venetoclax at same dose.

Second occurrence

Interrupt CALQUENCE and venetoclax until resolution of bleeding and thrombocytopenia resolves to Grade ≤ 1 or baseline.

Restart CALQUENCE at same dose and/or restart venetoclax at one lower dose level.e

Subsequent occurrences of severe thrombocytopenia

Interrupt CALQUENCE and venetoclax until resolution of bleeding and thrombocytopenia resolves to Grade ≤ 1 or baseline.

Restart CALQUENCE at a reduced frequency of 100 mg once daily and/or venetoclax at one lower dose level.c,d,e

Grade 3 or 4 tumour lysis syndrome (TLS)

First and subsequent episodes

If a subject experiences blood chemistry changes suggestive of TLS, the following day’s venetoclax and acalabrutinib dose should be withheld. If resolved within 24–48 hours of last dose, treatment can be resumed at the same dose.

For events of clinical TLS or blood chemistry changes requiring more than 48 hours to resolve, venetoclax should be resumed at one lower dose level.c When resuming treatment after interruption due to TLS, monitor for TLS and provide prophylaxis.

Grade 3 other non-hematologic eventsg

First occurrence

Interrupt CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1.

Restart CALQUENCE and/or venetoclax at same dose.

Second occurrence

Interrupt CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1d.

Grade 4 other non-hematologic eventsg

First occurrence

Interrupt CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1. Restart CALQUENCE at a reduced frequency of 100 mg once daily and/or venetoclax at one lower dose level.c, e

Second occurrence

Interrupt CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1d.

a Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

b Growth factor may be used at physician discretion.

c See venetoclax USPI for dose level reductions details.

d Clinical judgment of the treating physician should guide the management plan of each patient based on the individual benefit/risk assessment for treatment with CALQUENCE in combination with venetoclax.

e CALQUENCE dose may be re-escalated at the discretion of the physician if patient tolerates a reduced dose for ≥4 weeks.

f Platelets may be used at physician discretion.

g Certain treatment-emergent non-hematologic AEs (e.g., venous thromboembolic events) may be managed and become clinically stable following medical intervention but may not improve to Grade ≤ 1 according to the NCI CTCAE definitions. In such cases, if a subject is clinically stable, resumption of CALQUENCE may be possible based on clinical judgement of the treating physician.

CYP3A

Co-administered Drug

Recommended CALQUENCE use

Inhibition

Strong CYP3A inhibitor

Avoid co-administration.

If these inhibitors will be used short-term (such as anti‑infectives for up to seven days), interrupt CALQUENCE.

After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.

Moderate CYP3A inhibitor

Reduce the CALQUENCE 100 mg every 12 hours dosage to 100 mg once daily.

Induction

Strong CYP3A inducer

Avoid co-administration.

If co-administration is unavoidable, increase CALQUENCE dosage to 200 mg approximately every 12 hours.

Grade 3 or greater non-hematologic toxicities,

Grade 3 thrombocytopenia with bleeding,

Grade 4 thrombocytopenia or

Grade 4 neutropenia lasting longer than 7 days

First and Second

Interrupt CALQUENCE.

Once toxicity has resolved to Grade 1 or baseline level, CALQUENCE may be resumed at 100 mg approximately every 12 hours.

Third

Interrupt CALQUENCE.

Once toxicity has resolved to Grade 1 or baseline level, CALQUENCE may be resumed at a reduced frequency of 100 mg once daily.

Fourth

Discontinue CALQUENCE.

Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

Adverse Reaction

Severity^a

Dosage Modification

(Starting dosage of CALQUENCE = 100 mg approximately every 12 hours)

Neutropenia^b [see Warnings and Precautions (5.3)]

Absolute neutrophil count less than 0.5 x 10⁹/L for greater than 7 days

Interrupt CALQUENCE. Once toxicity has resolved to Grade ≤ 2, resume CALQUENCE at starting dosage.

Upon 2nd or 3rd occurrence, reduce dosage of CALQUENCE to 100 mg once daily.^c

Discontinue CALQUENCE at 4th occurrence.

For bendamustine^b :

Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2, resume bendamustine and consider dosage reduction to 70 mg/m^2.d,e

Thrombocytopenia^f [see Warnings and Precautions (5.3)]

Platelet count 25 to 50 x 10⁹/L with clinically significant bleeding or platelet count less than 25 x 10⁹/L

Interrupt CALQUENCE. Once toxicity has resolved to Grade ≤ 2 or baseline, resume CALQUENCE at starting dosage.

If recurrence, reduce dosage of CALQUENCE to 100 mg once daily.^c

Consider discontinuing CALQUENCE at 3rd occurrence.

For bendamustinef:

Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2 or baseline, resume bendamustine and consider dose reduction to 70 mg/m^2.e

Non-hematologic adverse reactions [see Warnings and Precautions (5)]

Grade 3 or higher

Interrupt CALQUENCE. Once toxicity has resolved to Grade ≤ 2 or baseline, resume CALQUENCE at starting dosage.

If recurrence, reduce dosage of CALQUENCE to 100 mg once daily.^c

Discontinue CALQUENCE at 3rd occurrence of Grade 4 toxicity. For Grade 3 toxicity, consider the risks and benefits of continuing CALQUENCE.

For bendamustine:

Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2 or baseline, resume bendamustine and consider dose reduction to 70 mg/m^2.e

^a Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

^b For neutropenia with ANC less than 1 x 10⁹/L, consideration for bendamustine dose interruption and dosage reduction to 70 mg/m² may be appropriate in certain circumstances.

^c Dose may be re-escalated at the discretion of the physician if patient tolerates a reduced dose for ≥4 weeks.

^d Consider use of myeloid growth factors before bendamustine dosage reduction.

^e Consider discontinuing bendamustine if additional dosage reduction is required.

^f For thrombocytopenia, a platelet count below 50 x 10⁹/L should prompt bendamustine dose interruption even in the absence of clinically significant bleeding.

Adverse Reactiona

Adverse Reaction Occurrence

Dose Modification

Grade 3 or 4 neutropenia with or without fever and/or infection; Grade 4 neutropenia lasting more than 7 days

First occurrence

Interrupt CALQUENCE and/or venetoclax.b

Once toxicity resolves to Grade ≤ 1 or baseline, restart CALQUENCE and/or venetoclax at same dose.

Second occurrence

Interrupt CALQUENCE and/or venetoclax.b

Once toxicity resolves to Grade ≤ 1 or baseline, restart CALQUENCE at same dose and venetoclax at one lower dose levelc.

Subsequent occurrence

Withhold CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1 or baseline.b,d

Grade 3 or 4 thrombocytopenia and/or bleedingf

First occurrence

Interrupt CALQUENCE and/or venetoclax. When bleeding resolves and thrombocytopenia is Grade ≤ 1 or baseline without transfusion support for 5 consecutive days, restart CALQUENCE and/or venetoclax at same dose.

Second occurrence

Interrupt CALQUENCE and venetoclax until resolution of bleeding and thrombocytopenia resolves to Grade ≤ 1 or baseline.

Restart CALQUENCE at same dose and/or restart venetoclax at one lower dose level.e

Subsequent occurrences of severe thrombocytopenia

Interrupt CALQUENCE and venetoclax until resolution of bleeding and thrombocytopenia resolves to Grade ≤ 1 or baseline.

Restart CALQUENCE at a reduced frequency of 100 mg once daily and/or venetoclax at one lower dose level.c,d,e

Grade 3 or 4 tumour lysis syndrome (TLS)

First and subsequent episodes

If a subject experiences blood chemistry changes suggestive of TLS, the following day’s venetoclax and acalabrutinib dose should be withheld. If resolved within 24–48 hours of last dose, treatment can be resumed at the same dose.

For events of clinical TLS or blood chemistry changes requiring more than 48 hours to resolve, venetoclax should be resumed at one lower dose level.c When resuming treatment after interruption due to TLS, monitor for TLS and provide prophylaxis.

Grade 3 other non-hematologic eventsg

First occurrence

Interrupt CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1.

Restart CALQUENCE and/or venetoclax at same dose.

Second occurrence

Interrupt CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1d.

Grade 4 other non-hematologic eventsg

First occurrence

Interrupt CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1. Restart CALQUENCE at a reduced frequency of 100 mg once daily and/or venetoclax at one lower dose level.c, e

Second occurrence

Interrupt CALQUENCE and/or venetoclax until toxicity resolves to Grade ≤ 1d.

a Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

b Growth factor may be used at physician discretion.

c See venetoclax USPI for dose level reductions details.

d Clinical judgment of the treating physician should guide the management plan of each patient based on the individual benefit/risk assessment for treatment with CALQUENCE in combination with venetoclax.

e CALQUENCE dose may be re-escalated at the discretion of the physician if patient tolerates a reduced dose for ≥4 weeks.

f Platelets may be used at physician discretion.

g Certain treatment-emergent non-hematologic AEs (e.g., venous thromboembolic events) may be managed and become clinically stable following medical intervention but may not improve to Grade ≤ 1 according to the NCI CTCAE definitions. In such cases, if a subject is clinically stable, resumption of CALQUENCE may be possible based on clinical judgement of the treating physician.

CYP3A

Co-administered Drug

Recommended CALQUENCE use

Inhibition

Strong CYP3A inhibitor

Avoid co-administration.

If these inhibitors will be used short-term (such as anti‑infectives for up to seven days), interrupt CALQUENCE.

After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.

Moderate CYP3A inhibitor

Reduce the CALQUENCE 100 mg every 12 hours dosage to 100 mg once daily.

Induction

Strong CYP3A inducer

Avoid co-administration.

If co-administration is unavoidable, increase CALQUENCE dosage to 200 mg approximately every 12 hours.