Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Contraindications

Children under 18 years
Chronic infection
Within 4 weeks of live viral or bacterial vaccination
Breastfeeding
Cerebrovascular disorder
Decompensated cardiac failure
Galactosaemia
History of cardiac arrest
History of cardiac failure
Immunodeficiency syndromes
Ischaemic heart disease
Long QT syndrome
Malignant neoplasm
Moderate hepatic impairment
New York Heart Association class III failure
New York Heart Association class IV failure
Non-paced sinus node dysfunction
Pregnancy
Second degree atrioventricular block
Third degree atrioventricular block
Torsade de pointes
Uncontrolled hypertension
Unstable angina
Within 6 months of a myocardial infarction
Within 6 months of a transient ischaemic attack

Precautions and Warnings

Elderly
Family history of long QT syndrome
Females of childbearing potential
Atrial fibrillation
Atrial flutter
Bradycardia
Diabetes mellitus
Electrolyte imbalance
First degree atrioventricular block
Glucose-galactose malabsorption syndrome
History of severe hepatic disorder
History of torsade de pointes
Lactose intolerance
Pulmonary fibrosis
QTc interval greater than or equal to 500 msec
Recurrent syncope
Severe obstructive pulmonary disease
Severe respiratory disease
Sinus bradycardia
Uveitis

Correct electrolyte disorders before treatment
Obtain ECG 4 hours after first dose in patients with cardiac conditions
Postpone treatment if there is active or suspected infection
First dose may cause bradycardia and heart block
Treatment to be initiated and supervised by a specialist
Varicella vaccination recommended for antibody-negative patients
Contains lactose
Ensure negative pregnancy test in week preceding initiation of treatment
Monitor serum transaminases before treatment
Perform ECG before treatment
Perform full blood count before treatment
Discontinue treatment immediately if pregnancy is suspected
If visual disturbances occur, perform ophthalmic evaluation
Monitor bilirubin levels before treatment
Monitor blood pressure regularly
Monitor ECG in patients at risk of QT prolongation
Monitor serum electrolytes
May reduce effectiveness of vaccinations during treatment
Risk of developing opportunistic infections
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if macular oedema occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Interrupt therapy if lymphocyte count less than 0.2 x10 to the power of 9/L
Interrupt treatment if severe infection develops
Female: Contraception required during and for 1 week after treatment
Advise patient to avoid exposure to direct sunlight

Ponesimod treatment may result in a transient decrease in heart rate (HR) and atrioventricular (AV) conduction delays, an up-titration scheme must therefore be used to reach the maintenance dose of 20mg once daily.

Temporary interruption of beta-blocker treatment may be needed prior to the initiation of ponesimod.

Four hour monitoring following the first dose of ponesimod is recommended in patients with sinus bradycardia, first or second degree AV block, or history of myocardial infarction or heart failure occurring more than 6 months prior to treatment initiation and in a stable condition. Four hour monitoring for signs and symptoms of bradycardia should include a minimum of hourly pulse and blood pressure measurements. At the end of the 4 hour observation, obtain an ECG. Additional monitoring after the 4 hour period is required if:
HR 4 hours post dose is less than 45 beats per minute,
HR 4 hours post dose is at lowest value post dose, suggesting that the maximum pharmacodynamic effect on the heart may not have occurred or,
The ECG 4 hours post dose shown new onset of second degree or higher AV block, continue to monitor until abnormalities are resolved. If pharmacological treatment is required, continue monitoring overnight and repeat 4 hour monitoring after the second dose.

Treatment of ponesimod should be delayed for 4 weeks after vaccination to allow for full effect.

Use immunosuppressants with caution up to a week after the last dose of ponesimod due to additive effect on the immune system.

Perform regular examinations of the fundus, including the macula, prior to treatment initiation of ponesimod and follow up evaluations during therapy in patients with history of uveitis and patients with diabetes mellitus. This is due to an increase risk of macular oedema during therapy with S1P receptor modulators.

Perform spirometry evaluation of respiratory function during therapy with ponesimod when clinically indicated.

Monitor for hepatotoxicity if patient develops symptoms suggestive of hepatic dysfunction.

Patients receiving ponesimod should not receive concomitant phototherapy with UV-B-radiation or PUVA-photochemotherapy.

If unexpected neurological or psychiatric symptoms occur, complete physical and neurological examination and consider a MRI.

Pregnancy and Lactation

Pregnancy

Ponesimod is contraindicated during pregnancy.

Use of ponesimod during pregnancy is contraindicated by the manufacturer. Animal studies have shown reproductive toxicity. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Ponesimod is contraindicated during breastfeeding.

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

Side Effects

Alanine aminotransferase increased
Anxiety
Arthralgia
Aspartate aminotransferase increased
Back pain
Bradycardia
Bronchitis
Cough
Depression
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Fatigue
Herpes zoster
Hypercholesterolaemia
Hyperkalaemia
Hypertension
Hypoaesthesia
Increase in plasma cholesterol
Increase of liver transaminases
Increases in hepatic enzymes
Influenza
Insomnia
Joint swelling
Laryngitis
Ligament injury
Lymphopenia
Macular oedema
Migraine
Nasopharyngitis
Painful extremities
Pharyngitis
Pneumonia
Pyrexia
Raised C-reactive protein
Reduced lymphocyte count
Respiratory tract infection
Rhinitis
Sinusitis
Somnolence
Upper respiratory tract infection
Urinary tract infections
Vertigo
Viral infection

Presentation

Oral formulations containing ponesimod.

Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Dosage

Adults

Additional Dosage Information

Contraindications

Children under 18 years
Chronic infection
Within 4 weeks of live viral or bacterial vaccination
Breastfeeding
Cerebrovascular disorder
Decompensated cardiac failure
Galactosaemia
History of cardiac arrest
History of cardiac failure
Immunodeficiency syndromes
Ischaemic heart disease
Long QT syndrome
Malignant neoplasm
Moderate hepatic impairment
New York Heart Association class III failure
New York Heart Association class IV failure
Non-paced sinus node dysfunction
Pregnancy
Second degree atrioventricular block
Third degree atrioventricular block
Torsade de pointes
Uncontrolled hypertension
Unstable angina
Within 6 months of a myocardial infarction
Within 6 months of a transient ischaemic attack

Precautions and Warnings

Elderly
Family history of long QT syndrome
Females of childbearing potential
Atrial fibrillation
Atrial flutter
Bradycardia
Diabetes mellitus
Electrolyte imbalance
First degree atrioventricular block
Glucose-galactose malabsorption syndrome
History of severe hepatic disorder
History of torsade de pointes
Lactose intolerance
Pulmonary fibrosis
QTc interval greater than or equal to 500 msec
Recurrent syncope
Severe obstructive pulmonary disease
Severe respiratory disease
Sinus bradycardia
Uveitis

Correct electrolyte disorders before treatment
Obtain ECG 4 hours after first dose in patients with cardiac conditions
Postpone treatment if there is active or suspected infection
First dose may cause bradycardia and heart block
Treatment to be initiated and supervised by a specialist
Varicella vaccination recommended for antibody-negative patients
Contains lactose
Ensure negative pregnancy test in week preceding initiation of treatment
Monitor serum transaminases before treatment
Perform ECG before treatment
Perform full blood count before treatment
Discontinue treatment immediately if pregnancy is suspected
If visual disturbances occur, perform ophthalmic evaluation
Monitor bilirubin levels before treatment
Monitor blood pressure regularly
Monitor ECG in patients at risk of QT prolongation
Monitor serum electrolytes
May reduce effectiveness of vaccinations during treatment
Risk of developing opportunistic infections
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if macular oedema occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Interrupt therapy if lymphocyte count less than 0.2 x10 to the power of 9/L
Interrupt treatment if severe infection develops
Female: Contraception required during and for 1 week after treatment
Advise patient to avoid exposure to direct sunlight

Ponesimod treatment may result in a transient decrease in heart rate (HR) and atrioventricular (AV) conduction delays, an up-titration scheme must therefore be used to reach the maintenance dose of 20mg once daily.

Temporary interruption of beta-blocker treatment may be needed prior to the initiation of ponesimod.

Four hour monitoring following the first dose of ponesimod is recommended in patients with sinus bradycardia, first or second degree AV block, or history of myocardial infarction or heart failure occurring more than 6 months prior to treatment initiation and in a stable condition. Four hour monitoring for signs and symptoms of bradycardia should include a minimum of hourly pulse and blood pressure measurements. At the end of the 4 hour observation, obtain an ECG. Additional monitoring after the 4 hour period is required if:
HR 4 hours post dose is less than 45 beats per minute,
HR 4 hours post dose is at lowest value post dose, suggesting that the maximum pharmacodynamic effect on the heart may not have occurred or,
The ECG 4 hours post dose shown new onset of second degree or higher AV block, continue to monitor until abnormalities are resolved. If pharmacological treatment is required, continue monitoring overnight and repeat 4 hour monitoring after the second dose.

Treatment of ponesimod should be delayed for 4 weeks after vaccination to allow for full effect.

Use immunosuppressants with caution up to a week after the last dose of ponesimod due to additive effect on the immune system.

Perform regular examinations of the fundus, including the macula, prior to treatment initiation of ponesimod and follow up evaluations during therapy in patients with history of uveitis and patients with diabetes mellitus. This is due to an increase risk of macular oedema during therapy with S1P receptor modulators.

Perform spirometry evaluation of respiratory function during therapy with ponesimod when clinically indicated.

Monitor for hepatotoxicity if patient develops symptoms suggestive of hepatic dysfunction.

Patients receiving ponesimod should not receive concomitant phototherapy with UV-B-radiation or PUVA-photochemotherapy.

If unexpected neurological or psychiatric symptoms occur, complete physical and neurological examination and consider a MRI.

Pregnancy and Lactation

Pregnancy

Ponesimod is contraindicated during pregnancy.

Use of ponesimod during pregnancy is contraindicated by the manufacturer. Animal studies have shown reproductive toxicity. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Ponesimod is contraindicated during breastfeeding.

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

Side Effects

Alanine aminotransferase increased
Anxiety
Arthralgia
Aspartate aminotransferase increased
Back pain
Bradycardia
Bronchitis
Cough
Depression
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Fatigue
Herpes zoster
Hypercholesterolaemia
Hyperkalaemia
Hypertension
Hypoaesthesia
Increase in plasma cholesterol
Increase of liver transaminases
Increases in hepatic enzymes
Influenza
Insomnia
Joint swelling
Laryngitis
Ligament injury
Lymphopenia
Macular oedema
Migraine
Nasopharyngitis
Painful extremities
Pharyngitis
Pneumonia
Pyrexia
Raised C-reactive protein
Reduced lymphocyte count
Respiratory tract infection
Rhinitis
Sinusitis
Somnolence
Upper respiratory tract infection
Urinary tract infections
Vertigo
Viral infection

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: November 2021

Reference Sources

Summary of Product Characteristics: Ponvory 20mg film coated tablets. Janssen-Cilag Ltd. Revised July 2021.
Summary of Product Characteristics: Ponvory 2mg, 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, 10mg film coated tablets (treatment initiation pack). Janssen-Cilag Ltd. Revised July 2021.