Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease as defined by clinical or imaging features.

Contraindications

Children under 18 years
Chronic infection
Severe infection
Breastfeeding
Cerebrovascular accident
Decompensated cardiac failure
Hepatitis
History of atrioventricular block
Immunodeficiency syndromes
Long QT syndrome
Malignant neoplasm
New York Heart Association class III failure
New York Heart Association class IV failure
Non-paced second degree atrioventricular block
Non-paced sinus node dysfunction
Non-paced third degree atrioventricular block
Pregnancy
Severe hepatic impairment
Torsade de pointes
Transient ischaemic attack
Tuberculosis
Unstable angina
Within 6 months of a myocardial infarction

Precautions and Warnings

Family history of long QT syndrome
Females of childbearing potential
History of immunosuppressant treatment
Patients over 55 years
Predisposition to infection
Predisposition to prolongation of QT interval
Predisposition to uveitis
Bradycardia
Cerebrovascular disorder
Chronic obstructive pulmonary disease
Diabetes mellitus
Electrolyte imbalance
Hepatic impairment
History of cardiac arrest
History of cardiac failure
History of retinal disorder
History of torsade de pointes
Pulmonary fibrosis
QTc interval greater than or equal to 500 msec
Recurrent syncope
Severe respiratory disease
Severe sleep apnoea
Uncontrolled hypertension

Correct electrolyte disorders before treatment
Do not administer if live vaccine given within last 30 days
Live virus vaccine should not be given for 3 months after treatment
Postpone treatment if there is active or suspected infection
Treatment to be initiated and supervised by a specialist
Blood counts should be performed before and periodically during treatment
Ensure negative pregnancy test in week preceding initiation of treatment
Perform ECG before treatment
Monitor blood pressure regularly
Monitor ECG in patients at risk of QT prolongation
Monitor for bradycardia for 6 hours after first dose if HR < 55 bpm
Monitor liver function if anorexia,nausea,vomiting,abdominal pain develop
Monitor patient closely during drug discontinuation for rebound effect
Monitor serum electrolytes
Monitor transaminases/bilirubin at 1 month and every 3 months for 1 year
Advise patient to report new visual problems and symptoms
Advise patient to report symptoms of infection immediately
Consider discontinuing treatment if serious infection occurs
Immunosuppressive drugs may increase risk of malignancy
Risk of developing opportunistic infections
Discontinue if macular oedema occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if signs or symptoms of hepatic injury occur
Interrupt therapy if hepatic transaminases > 5 times upper limit of normal
Interrupt therapy if lymphocyte count less than 0.2 x10 to the power of 9/L
Female: Contraception required during and for 3 months after treatment
Advise patient to avoid exposure to direct sunlight

In patients with a resting heart rate less than 55 beats per minute, second-degree atrioventricular block or a history of myocardial infarction or heart failure, 6 hour monitoring for signs and symptoms of symptomatic bradycardia is recommended following first dose of ozanimod.

Additional monitoring after 6 hours is recommended in patients with a heart rate less than 45 beats per minute or if there is evidence of a new onset second-degree or higher atrioventricular block at the 6 hour post dose ECG. Appropriate management should be initiated and monitoring continued until the symptoms/findings have resolved. If required, monitoring should be continued overnight with a repeated 6 hour monitoring period following the second dose of ozanimod.

Monitor for infections for up to 3 months following the discontinuation of ozanimod.

There is an increased risk of immunosuppression if ozanimod is taken concurrently with antineoplastic, immunosuppressive or immune-modulating therapies. The half life and mode of action must be considered when switching to ozanimod from immunosuppressive products to minimize the risk of disease reactivation.

Physicians should be vigilant for symptoms or MRI findings suggestive of progressive multifocal leukoencephalopathy (PML).

Pregnancy and Lactation

Pregnancy

Ozanimod is contraindicated during pregnancy.

Use of ozanimod during pregnancy is contraindicated by the manufacturer. A negative pregnancy test result must be available prior to treatment with ozanimod. Ozanimod should be stopped 3 months before planning a pregnancy, if a woman becomes pregnant during treatment, ozanimod must be discontinued. Animal studies have shown reproductive toxicity. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Ozanimod is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking ozanimod. Animal data reports levels of ozanimod in the breast milk, however presence in human breast milk and the effects on exposed infants are unknown.

Side Effects

Alanine aminotransferase increased
Bradyarrhythmias
Bradycardia
Gamma glutamyl transferase (GGT) increased
Herpes zoster
Hypersensitivity reactions
Hypertension
Increased blood pressure
Increases in hepatic enzymes
Lymphopenia
Macular oedema
Nasopharyngitis
Orthostatic hypotension
Pharyngitis
Pulmonary function test abnormal
Rash
Reduced lymphocyte count
Respiratory tract infection
Serum bilirubin increased
Urinary tract infections
Urticaria

Presentation

Oral formulations of ozanimod.

Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease as defined by clinical or imaging features.

Dosage

Adults

Contraindications

Children under 18 years
Chronic infection
Severe infection
Breastfeeding
Cerebrovascular accident
Decompensated cardiac failure
Hepatitis
History of atrioventricular block
Immunodeficiency syndromes
Long QT syndrome
Malignant neoplasm
New York Heart Association class III failure
New York Heart Association class IV failure
Non-paced second degree atrioventricular block
Non-paced sinus node dysfunction
Non-paced third degree atrioventricular block
Pregnancy
Severe hepatic impairment
Torsade de pointes
Transient ischaemic attack
Tuberculosis
Unstable angina
Within 6 months of a myocardial infarction

Precautions and Warnings

Family history of long QT syndrome
Females of childbearing potential
History of immunosuppressant treatment
Patients over 55 years
Predisposition to infection
Predisposition to prolongation of QT interval
Predisposition to uveitis
Bradycardia
Cerebrovascular disorder
Chronic obstructive pulmonary disease
Diabetes mellitus
Electrolyte imbalance
Hepatic impairment
History of cardiac arrest
History of cardiac failure
History of retinal disorder
History of torsade de pointes
Pulmonary fibrosis
QTc interval greater than or equal to 500 msec
Recurrent syncope
Severe respiratory disease
Severe sleep apnoea
Uncontrolled hypertension

Correct electrolyte disorders before treatment
Do not administer if live vaccine given within last 30 days
Live virus vaccine should not be given for 3 months after treatment
Postpone treatment if there is active or suspected infection
Treatment to be initiated and supervised by a specialist
Blood counts should be performed before and periodically during treatment
Ensure negative pregnancy test in week preceding initiation of treatment
Perform ECG before treatment
Monitor blood pressure regularly
Monitor ECG in patients at risk of QT prolongation
Monitor for bradycardia for 6 hours after first dose if HR < 55 bpm
Monitor liver function if anorexia,nausea,vomiting,abdominal pain develop
Monitor patient closely during drug discontinuation for rebound effect
Monitor serum electrolytes
Monitor transaminases/bilirubin at 1 month and every 3 months for 1 year
Advise patient to report new visual problems and symptoms
Advise patient to report symptoms of infection immediately
Consider discontinuing treatment if serious infection occurs
Immunosuppressive drugs may increase risk of malignancy
Risk of developing opportunistic infections
Discontinue if macular oedema occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if signs or symptoms of hepatic injury occur
Interrupt therapy if hepatic transaminases > 5 times upper limit of normal
Interrupt therapy if lymphocyte count less than 0.2 x10 to the power of 9/L
Female: Contraception required during and for 3 months after treatment
Advise patient to avoid exposure to direct sunlight

In patients with a resting heart rate less than 55 beats per minute, second-degree atrioventricular block or a history of myocardial infarction or heart failure, 6 hour monitoring for signs and symptoms of symptomatic bradycardia is recommended following first dose of ozanimod.

Additional monitoring after 6 hours is recommended in patients with a heart rate less than 45 beats per minute or if there is evidence of a new onset second-degree or higher atrioventricular block at the 6 hour post dose ECG. Appropriate management should be initiated and monitoring continued until the symptoms/findings have resolved. If required, monitoring should be continued overnight with a repeated 6 hour monitoring period following the second dose of ozanimod.

Monitor for infections for up to 3 months following the discontinuation of ozanimod.

There is an increased risk of immunosuppression if ozanimod is taken concurrently with antineoplastic, immunosuppressive or immune-modulating therapies. The half life and mode of action must be considered when switching to ozanimod from immunosuppressive products to minimize the risk of disease reactivation.

Physicians should be vigilant for symptoms or MRI findings suggestive of progressive multifocal leukoencephalopathy (PML).

Pregnancy and Lactation

Pregnancy

Ozanimod is contraindicated during pregnancy.

Use of ozanimod during pregnancy is contraindicated by the manufacturer. A negative pregnancy test result must be available prior to treatment with ozanimod. Ozanimod should be stopped 3 months before planning a pregnancy, if a woman becomes pregnant during treatment, ozanimod must be discontinued. Animal studies have shown reproductive toxicity. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Ozanimod is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking ozanimod. Animal data reports levels of ozanimod in the breast milk, however presence in human breast milk and the effects on exposed infants are unknown.

Side Effects

Alanine aminotransferase increased
Bradyarrhythmias
Bradycardia
Gamma glutamyl transferase (GGT) increased
Herpes zoster
Hypersensitivity reactions
Hypertension
Increased blood pressure
Increases in hepatic enzymes
Lymphopenia
Macular oedema
Nasopharyngitis
Orthostatic hypotension
Pharyngitis
Pulmonary function test abnormal
Rash
Reduced lymphocyte count
Respiratory tract infection
Serum bilirubin increased
Urinary tract infections
Urticaria

Overdosage

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: December 2020.

Reference Sources

Summary of Product Characteristics: Zeposia hard capsules. Bristol-Myers Squibb Pharmaceuticals Limited. Revised October 2020.