Drugs List

Therapeutic Indications

Uses

Prevention of recurrence of non-permanent atrial fibrillation

Maintenance of sinus rhythm after successful cardioversion in adult clinically stable patients with paroxysmal or persistent atrial fibrillation.

Dronedarone should only be prescribed after alternative treatment options have been considered.

Contraindications

Children under 18 years
Sinus node dysfunction
Bradycardia with pulse rate at rest < 50 beats per minute
Breastfeeding
Bundle branch block
Cardiac failure
Galactosaemia
Haemodynamic instability
History of cardiac failure
History of hepatotoxicity secondary to amiodarone
History of pulmonary toxicity secondary to amiodarone
Left ventricular dysfunction
Long QT syndrome
Non paced atrial conduction defects
Non paced second/third degree AV block
Non-paced sinus node dysfunction
Pregnancy
QTc interval greater than or equal to 500 msec
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Females of childbearing potential
Patients over 75 years
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Hypokalaemia
Hypomagnesaemia
Ischaemic heart disease
Lactose intolerance

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated by specialist
Contains lactose
Monitor creatinine prior to & after 7 days & then use as baseline value
Perform ECG before and during treatment
Perform liver function tests before commencing therapy
If serum creatinine is raised at day 7, recheck at day 14
Monitor renal function regularly
Monitor serum electrolytes
Perform LFTs 1 week and 1 month after initiation then monthly for 6 months
Perform LFTs at months 9 and 12 and periodically thereafter
Advise patient to report new or worsening signs of cardiac failure
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Consider discontinuation if serum creatinine continues to rise
Discontinue at the first signs of cardiac failure
Discontinue if ALT level exceeds 3 times the upper limit of normal
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if left ventricular systolic dysfunction develops
Discontinue if permanent atrial fibrillation occurs
Discontinue if pulmonary toxicity occurs
Discontinue treatment if QTc exceeds 500msec
Advise patient not to take simvastatin unless advised by clinician
Advise patient not to take St John's wort concurrently
Grapefruit juice should not be taken simultaneously
Female: Ensure adequate contraception during treatment

Perform ECGs serially, at least every 6 months.

If alanine transaminase (ALT) levels are elevated to greater than or equal to 3 times the upper limit of normal (ULN), levels should be remeasured within 48 to 72 hours. If ALT levels are confirmed to be greater than or equal to 3 times ULN, after remeasurement, dronedarone should be withdrawn. Appropriate investigation and close observation of patients should continue until normalisation of ALT. Advise patients to immediately report symptoms of hepatic injury (such as sustained new onset abdominal pain, anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine or itching).

Increases in plasma creatinine levels have been observed in healthy subjects and in patients taking dronedarone 400mg twice daily. This increase occurs early after treatment initiation and reaches a plateau after 7 days. Patients should have their plasma creatinine levels measured prior to and 7 days after initiation. If an increase in creatinine is observed, serum creatinine should be re-measured after a further 7 days. If no further increase is observed, this value should be used as the new reference baseline. Renal function should be monitored periodically thereafter. If serum creatinine continues to rise then consideration should be given to further investigation and discontinuing treatment.

An increase in creatinine should not necessarily lead to the discontinuation of treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists.

Dronedarone may induce moderate QTc prolongation (about 10msec), related to prolonged repolarisation. These changes are linked to the therapeutic effect of dronedarone and do not reflect toxicity. Follow up, including ECG is recommended during treatment. If the QTc interval is greater than or equal to 500milliseconds then treatment with dronedarone should be stopped.

Interstitial lung disease including pneumonitis and pulmonary fibrosis have been reported. Onset of dyspnoea or non productive cough may be related to pulmonary toxicity and patients should be carefully evaluated. If pulmonary toxicity is confirmed treatment should be discontinued.

Patients should be appropriately anticoagulated in accordance with current clinical guidelines. The INR should be closely monitored after initiation of dronedarone in patients taking vitamin K antagonists, see specific product literature.

Pregnancy and Lactation

Pregnancy

Dronedarone is contraindicated during pregnancy.

The manufacturer does not recommend using dronedarone during pregnancy or in women of childbearing potential not using contraception. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Dronedarone is contraindicated for use during breastfeeding.

The manufacturer advises that the patient either discontinues dronedarone or discontinues breastfeeding. Animal data reports dronedarone is excreted in the breast milk, however presence in human breast milk and the effects on exposed infants are unknown.

Side Effects

Abdominal pain
Abnormal liver function tests
Ageusia
Allergic dermatitis
Anaphylaxis
Angioedema
Asthenia
Bradycardia
Congestive cardiac failure
Dermatitis
Diarrhoea
Dysgeusia
Dyspepsia
Eczema
Erythema
Fatigue
Gastro-intestinal disturbances
Hepatic failure
Hepatocellular damage
Interstitial lung disease
Leukocytoclastic vasculitis
Malaise
Nausea
Photosensitivity
Pneumonitis
Prolongation of QT interval
Pruritus
Pulmonary fibrosis
Rash
Serum creatinine increased
Vasculitis
Vomiting

Presentation

Oral formulations of dronedarone.

Drugs List

Therapeutic Indications

Uses

Prevention of recurrence of non-permanent atrial fibrillation

Maintenance of sinus rhythm after successful cardioversion in adult clinically stable patients with paroxysmal or persistent atrial fibrillation.

Dronedarone should only be prescribed after alternative treatment options have been considered.

Dosage

Adults

Additional Dosage Information

Contraindications

Children under 18 years
Sinus node dysfunction
Bradycardia with pulse rate at rest < 50 beats per minute
Breastfeeding
Bundle branch block
Cardiac failure
Galactosaemia
Haemodynamic instability
History of cardiac failure
History of hepatotoxicity secondary to amiodarone
History of pulmonary toxicity secondary to amiodarone
Left ventricular dysfunction
Long QT syndrome
Non paced atrial conduction defects
Non paced second/third degree AV block
Non-paced sinus node dysfunction
Pregnancy
QTc interval greater than or equal to 500 msec
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Females of childbearing potential
Patients over 75 years
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Hypokalaemia
Hypomagnesaemia
Ischaemic heart disease
Lactose intolerance

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated by specialist
Contains lactose
Monitor creatinine prior to & after 7 days & then use as baseline value
Perform ECG before and during treatment
Perform liver function tests before commencing therapy
If serum creatinine is raised at day 7, recheck at day 14
Monitor renal function regularly
Monitor serum electrolytes
Perform LFTs 1 week and 1 month after initiation then monthly for 6 months
Perform LFTs at months 9 and 12 and periodically thereafter
Advise patient to report new or worsening signs of cardiac failure
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Consider discontinuation if serum creatinine continues to rise
Discontinue at the first signs of cardiac failure
Discontinue if ALT level exceeds 3 times the upper limit of normal
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if left ventricular systolic dysfunction develops
Discontinue if permanent atrial fibrillation occurs
Discontinue if pulmonary toxicity occurs
Discontinue treatment if QTc exceeds 500msec
Advise patient not to take simvastatin unless advised by clinician
Advise patient not to take St John's wort concurrently
Grapefruit juice should not be taken simultaneously
Female: Ensure adequate contraception during treatment

Perform ECGs serially, at least every 6 months.

If alanine transaminase (ALT) levels are elevated to greater than or equal to 3 times the upper limit of normal (ULN), levels should be remeasured within 48 to 72 hours. If ALT levels are confirmed to be greater than or equal to 3 times ULN, after remeasurement, dronedarone should be withdrawn. Appropriate investigation and close observation of patients should continue until normalisation of ALT. Advise patients to immediately report symptoms of hepatic injury (such as sustained new onset abdominal pain, anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine or itching).

Increases in plasma creatinine levels have been observed in healthy subjects and in patients taking dronedarone 400mg twice daily. This increase occurs early after treatment initiation and reaches a plateau after 7 days. Patients should have their plasma creatinine levels measured prior to and 7 days after initiation. If an increase in creatinine is observed, serum creatinine should be re-measured after a further 7 days. If no further increase is observed, this value should be used as the new reference baseline. Renal function should be monitored periodically thereafter. If serum creatinine continues to rise then consideration should be given to further investigation and discontinuing treatment.

An increase in creatinine should not necessarily lead to the discontinuation of treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists.

Dronedarone may induce moderate QTc prolongation (about 10msec), related to prolonged repolarisation. These changes are linked to the therapeutic effect of dronedarone and do not reflect toxicity. Follow up, including ECG is recommended during treatment. If the QTc interval is greater than or equal to 500milliseconds then treatment with dronedarone should be stopped.

Interstitial lung disease including pneumonitis and pulmonary fibrosis have been reported. Onset of dyspnoea or non productive cough may be related to pulmonary toxicity and patients should be carefully evaluated. If pulmonary toxicity is confirmed treatment should be discontinued.

Patients should be appropriately anticoagulated in accordance with current clinical guidelines. The INR should be closely monitored after initiation of dronedarone in patients taking vitamin K antagonists, see specific product literature.

Pregnancy and Lactation

Pregnancy

Dronedarone is contraindicated during pregnancy.

The manufacturer does not recommend using dronedarone during pregnancy or in women of childbearing potential not using contraception. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Dronedarone is contraindicated for use during breastfeeding.

The manufacturer advises that the patient either discontinues dronedarone or discontinues breastfeeding. Animal data reports dronedarone is excreted in the breast milk, however presence in human breast milk and the effects on exposed infants are unknown.

Side Effects

Abdominal pain
Abnormal liver function tests
Ageusia
Allergic dermatitis
Anaphylaxis
Angioedema
Asthenia
Bradycardia
Congestive cardiac failure
Dermatitis
Diarrhoea
Dysgeusia
Dyspepsia
Eczema
Erythema
Fatigue
Gastro-intestinal disturbances
Hepatic failure
Hepatocellular damage
Interstitial lung disease
Leukocytoclastic vasculitis
Malaise
Nausea
Photosensitivity
Pneumonitis
Prolongation of QT interval
Pruritus
Pulmonary fibrosis
Rash
Serum creatinine increased
Vasculitis
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: October 2019

Reference Sources

Summary of Products Characteristics: Multaq 400mg film coated tablets. Sanofi Aventis. Revised September 2019.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 14 October 2019