Ixazomib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ixazomib.
Drugs List
Therapeutic Indications
Uses
Multiple myeloma: resistant to one previous therapy
Ixazomib in combination with lenalidomide and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Treatment should be continued until disease progression or unacceptable toxicity. Limited data exists on the tolerability and toxicity of treatment beyond 24 cycles.
Adults
4mg of ixazomib administered once a week on days 1, 8 and 15 of a 28 day treatment cycle.
25mg of lenalidomide administered daily on days 1 to 21 of a 28 day treatment cycle.
40mg of dexamethasone administered once a week on days 1, 8, 15 and 22 of a 28 day treatment cycle.
Patients with Renal Impairment
Patients with severe renal impairment or end-stage renal disease requiring dialysis
3mg of ixazomib administered once a week on days 1, 8 and 15 of a 28 day treatment cycle.
Patients with Hepatic Impairment
Patients with moderate or severe hepatic impairment
3mg of ixazomib administered once a week on days 1, 8 and 15 of a 28 day treatment cycle.
Additional Dosage Information
Dose modifications may be required due to toxicity. Dose reductions are made in a step wise manner and in some cases are alternated between a reduction in lenalidomide dose and a reduction in ixazomib dose.
Dose reduction steps
Ixazomib
First dose reduction: Reduce to 3mg.
Second dose reduction: Reduce to 2.3mg.
Further dose reduction: Discontinue treatment.
Lenalidomide
Lenalidomide dose reductions should be made according to its manufacturer's recommendations.
Dose modifications for haematological toxicities
Platelet count below 30,0000 per cubic millimetre
At first occurrence: Withhold ixazomib and lenalidomide until platelet count returns to more than 30,0000 per cubic millimetre. Resume ixazomib at the same dose level and resume lenalidomide at one lower dose level.
At second occurrence: Withhold ixazomib and lenalidomide until platelet count returns to more than 30,000 per cubic millimetre. Resume ixazomib at one lower dose level, and resume lenalidomide at the same dose level.
Absolute neutrophil count below 500 per cubic millimetre
At first occurrence: Withhold ixazomib and lenalidomide until absolute neutrophil count is more than 500 per cubic millimetre. Resume ixazomib at the same dose level and resume lenalidomide at one lower dose level according to its manufacturer's recommendations. Consider adding G-CSF.
At second occurrence: Withhold ixazomib and lenalidomide until absolute neutrophil count is more than 500 per cubic millimetre. Resume ixazomib at one lower dose level and resume lenalidomide at the same dose level.
Dose modifications for non-haematological toxicities
Rash
Grade 2 or 3 rash: At first occurrence, withhold lenalidomide until rash recovers to grade 1 or below, then resume at one lower dose level. At second occurrence, withhold ixazomib and lenalidomide until rash recovers to grade 1 or below, then resume ixazomib at one lower dose level, and resume lenalidomide at the same dose level.
Grade 4 rash: Discontinue treatment.
Peripheral neuropathy
Grade 2 peripheral neuropathy (or grade 1 peripheral neuropathy with pain): Withhold ixazomib until peripheral neuropathy recovers to grade 1 without pain (or patients baseline), then resume ixazomib at the same dose level.
Grade 3 peripheral neuropathy (or grade 2 peripheral neuropathy with pain): Withhold ixazomib until peripheral neuropathy recovers to grade 1 without pain (or patients baseline), then resume ixazomib and reduce by one dose level.
Grade 4 peripheral neuropathy: Discontinue ixazomib treatment.
Other non-haematological toxicities
Grade 3 or 4 non-haematological toxicities: Withhold ixazomib until non-haematological toxicity recovers to grade 1 (or patients baseline). If non-haematological toxicity is attributable to ixazomib, resume treatment and reduce ixazomib by one dose level.
Delayed or missed doses
If a dose of ixazomib is delayed or missed, the dose should only be taken if the next scheduled dose is more than 72 hours away. A double dose should not be taken to make up for a missed dose. If a patient vomits after taking a dose, the patient should take the next scheduled dose at the appropriate time, and not repeat the dose.
Contraindications
Children under 18 years
Neutrophil count below 1 x 10 to the power of 9 / L on day 1 of cycle
Platelet count below 75 x 10 to the power of 9/L on day 1 of cycle
Breastfeeding
Pregnancy
Precautions and Warnings
Absolute neutrophil count below 0.5 x 10 to the power of 9 / L
Platelet count below 30 x 10 to the power of 9 / L
End stage renal disease
Moderate hepatic impairment
Peripheral neuropathy
Renal impairment - creatinine clearance below 30 ml/minute
Serum bilirubin above 1.5 times upper limit of normal
Reduce dose in patients on renal dialysis
Reduce dose in patients with creatinine clearance below 30ml/min
Reduce dose in patients with moderate hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Anti-emetics may be required during therapy
Consider use of anticoagulant prophylaxis if at risk of thromboembolism
Herpes zoster reactivation possible - consider antiviral prophylaxis
Prophylactic G-CSF should be considered
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor hepatic function before treatment and regularly during treatment
Monitor platelets before starting and during treatment
Monitor for symptoms of peripheral neuropathy
Monitor patients for signs of tumour lysis syndrome
Monitor serum potassium in patients with gastrointestinal conditions
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of thrombotic microangiopathy
Reduce dose if grade 3 or 4 gastrointestinal toxicities occur
Discontinue if grade 4 skin reaction occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue in grade 4 neuropathy
Suspend at first signs of thrombotic microangiopathy
Suspend therapy if neutrophils fall below 0.5 x 10 to the power of 9 / L
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Suspend treatment if platelet count below 30 x 10 to the power of 9/l
Suspend treatment or reduce dose if peripheral neuropathy occurs
Advise patient not to take St John's wort concurrently
Female: Effect of hormonal contraceptive may be reduced
Female:Barrier contraception required during & for 3 months after treatment
Male: Contraception required during and for 3 months after treatment
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.
In the case of severe gastrointestinal events, serum potassium should be monitored. Antiemetics and antidiarrhoeals may be required.
If a patient presents with peripheral oedema, they should be evaluated and treated for underlying causes. Dose adjustment should follow other non-haematological toxicities (see Dosage; Additional).
Pregnancy and Lactation
Pregnancy
Ixazomib is contraindicated in pregnancy.
There are no data for the use of ixazomib in pregnant women. Animal studies have shown reproductive toxicity. Ixazomib use in pregnancy is contraindicated by the manufacturer, based on the potential for harm to the foetus.
Lactation
Ixazomib is contraindicated in breastfeeding.
At the time of writing there is limited published information regarding the use of ixazomib during breastfeeding or in animal lactation studies. The manufacturer contraindicates breastfeeding during ixazomib therapy, as a risk to the nursing infant cannot be excluded.
LactMed suggests that ixazomib is likely to accumulate in the infant, due to its half-life of 9.5 days. LactMed recommends that breastfeeding should be discontinued during ixazomib therapy, and for 90 days after the last dose.
Side Effects
Acute febrile dermatosis (Sweet's syndrome)
Alterations in hepatic enzymes
Arrhythmias
Back pain
Blurred vision
Cardiac failure
Cataracts
Conjunctivitis
Constipation
Decreased appetite
Diarrhoea
Dry eyes
Fatigue
Hepatic impairment
Hepatotoxicity
Herpes zoster
Hypokalaemia
Hypotension
Nausea
Neutropenia
Peripheral neuropathy
Peripheral oedema
Posterior reversible encephalopathy syndrome (PRES)
Rash
Stevens-Johnson syndrome
Thrombocytopenia
Thrombotic microangiopathy
Thrombotic thrombocytopenic purpura
Transverse myelitis
Tumour lysis syndrome
Upper respiratory tract infection
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: May 2019.
Reference Sources
Summary of Product Characteristics: Ninlaro capsules. Takeda UK Ltd. Revised November 2020.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Ixazomib Last revised: 03 December 2018
Last accessed: 15 May 2019
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