Strattera® (atomoxetine): Cardiovascular

Pre-treatment screening:

Prior to prescribing it is necessary to take an appropriate medical history and conduct a baseline evaluation of a patient’s cardiovascular status, including blood pressure and heart rate.

Ongoing monitoring:

Cardiovascular status should be regularly monitored with blood pressure and pulse recorded after each adjustment of dose and then at least every 6 months. For paediatric patients the use of a centile chart is recommended. For adults, current reference guidelines for hypertension should be followed.

Atomoxetine should not be used in patients with severe cardiovascular or cerebrovascular disorders. Severe cardiovascular disorders may include severe hypertension, heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias and channelopathies (disorders caused by the dysfunction of ion channels). Severe cerebrovascular disorders may include cerebral aneurysm or stroke.

Atomoxetine should not be used in patients with pheochromocytoma or a history of pheochromocytoma.

Sudden death and pre-existing cardiac abnormalities:

Sudden death has been reported in patients with structural cardiac abnormalities who were taking atomoxetine at usual doses. Although some serious structural cardiac abnormalities alone carry an increased risk of sudden death, atomoxetine should only be used with caution in patients with known serious structural cardiac abnormalities and in consultation with a cardiac specialist.

Cardiovascular effects:

Atomoxetine can affect heart rate and blood pressure. Most patients taking atomoxetine experience a modest increase in heart rate (mean <10 bpm) and/or increase in blood pressure (mean <5 mm Hg).

However, combined data from controlled and uncontrolled ADHD clinical trials show that approximately 8-12% of children and adolescents, and 6-10% of adults experience more pronounced changes in heart rate (20 beats per minute or greater) and blood pressure (15-20 mmHg or greater). Analysis of these clinical trial data showed that approximately 15-26% of children and adolescents, and 27-32% of adults experiencing such changes in blood pressure and heart rate during atomoxetine treatment had sustained or progressive increases. Long-term sustained changes in blood pressure may potentially contribute to clinical consequences such as myocardial hypertrophy.

As a result of these findings, patients who are being considered for treatment with atomoxetine should have a careful history and physical exam to assess for the presence of cardiac disease, and should receive further specialist cardiac evaluation if initial findings suggest such history or disease.

It is recommended that heart rate and blood pressure be measured and recorded before treatment is started and, during treatment, after each adjustment of dose and then at least every 6 months to detect possible clinically important increases. For paediatric patients the use of a centile chart is recommended. For adults, current reference guidelines for hypertension should be followed.

Atomoxetine should not be used in patients with severe cardiovascular or cerebrovascular disorders. Atomoxetine should be used with caution in patients whose underlying medical conditions could be worsened by increases in blood pressure and heart rate, such as patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease.

Patients who develop symptoms such as palpitations, exertional chest pain, unexplained syncope, dyspnoea or other symptoms suggestive of cardiac disease during atomoxetine treatment should undergo a prompt specialist cardiac evaluation.

In addition, atomoxetine should be used with caution in patients with congenital or acquired long QT or a family history of QT prolongation.

As orthostatic hypotension has also been reported, atomoxetine should be used with caution in any condition that may predispose patients to hypotension or conditions associated with abrupt heart rate or blood pressure changes.

Cerebrovascular effects:

Patients with additional risk factors for cerebrovascular conditions (such as a history of cardiovascular disease, concomitant medications that elevate blood pressure) should be assessed at every visit for neurological signs and symptoms after initiating treatment with atomoxetine.

Effects of Other Drugs on Atomoxetine

Salbutamol (or other beta₂ agonists):

Atomoxetine should be administered with caution to patients treated with high dose nebulised or systemically administered salbutamol (or other beta₂ agonists) because cardiovascular effects can be potentiated.

Contradictory findings regarding this interaction were found. Systemically administered salbutamol (600 μg i.v. over 2 hrs) in combination with atomoxetine (60 mg twice daily for 5 days) induced increases in heart rate and blood pressure. This effect was most marked after the initial coadministration of salbutamol and atomoxetine but returned towards baseline at the end of 8 hours. However, in a separate study the effects on blood pressure and heart rate of a standard inhaled dose of salbutamol (200 μg) were not increased by the short-term coadministration of atomoxetine (80 mg once daily for 5 days) in a study of healthy Asian adults who were extensive atomoxetine metabolisers. Similarly, heart rate after multiple inhalations of salbutamol (800 μg) did not differ in the presence or absence of atomoxetine.

Attention should be paid to monitoring heart rate and blood pressure, and dose adjustments may be justified for either atomoxetine or salbutamol (or other beta₂ agonists) in the event of significant increases in heart rate and blood pressure during coadministration of these drugs.

There is the potential for an increased risk of QT interval prolongation when atomoxetine is administered with other QT prolonging drugs (such as neuroleptics, class IA and III anti-arrhythmics, moxifloxacin, erythromycin, methadone, mefloquine, tricyclic antidepressants, lithium, or cisapride), drugs that cause electrolyte imbalance (such as thiazide diuretics), and drugs that inhibit CYP2D6.

Anti-hypertensive drugs:

Atomoxetine should be used cautiously with anti-hypertensive drugs. Because of a possible increase in blood pressure, atomoxetine may decrease the effectiveness of anti-hypertensive drugs / drugs used to treat hypertension. Attention should be paid to monitoring of blood pressure and review of treatment of atomoxetine or anti-hypertensive drugs may be justified in the case of significant changes of blood pressure.

Pressor agents or drugs that increase blood pressure:

Because of possible increase in effects on blood pressure, atomoxetine should be used cautiously with pressor agents or medications that may increase blood pressure (such as salbutamol). Attention should be paid to monitoring of blood pressure, and review of treatment for either atomoxetine or pressor agents may be justified in the case of significant change in blood pressure.

Summary of the safety profile

In both paediatric and adult placebo-controlled trials, patients taking atomoxetine experienced increases in heart rate, systolic and diastolic blood pressure.

Because of its effect on noradrenergic tone, orthostatic hypotension (0.2%) and syncope (0.8%) have been reported in patients taking atomoxetine. Atomoxetine should be used with caution in any condition that may predispose patients to hypotension.

REFERENCE

Strattera Summary of Product Characteristics