Interactions : אינטראקציות

4.5     Interaction with other medicinal products and other forms of interaction

Effects of other drugs on atomoxetine
MAOIs
Atomoxetine should not be used with MAOIs (see section 4.3).

CYP2D6 inhibitors (SSRIs (e.g. fluoxetine, paroxetine), quinidine, terbinafine) In patients receiving these drugs, atomoxetine exposure may be 6-to 8-fold increased and Css max 3 to 4 times higher, because it is metabolised by the CYP2D6 pathway. Slower titration and final lower dosage of atomoxetine may be necessary in patients who are already taking CYP2D6 inhibitor drugs.
If a CYP2D6 inhibitor is prescribed or discontinued after titration to the appropriate atomoxetine dose 
has occurred, the clinical response and tolerability should be re-evaluated for that patient to determine if dose adjustment is needed.

Caution is advised when combining atomoxetine with potent inhibitors of cytochrome P450 enzymes other than CYP2D6 in patients who are poor CYP2D6 metabolisers as the risk of clinically relevant increases in atomoxetine exposure in vivo is unknown.

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.

Seizures are a potential risk with atomoxetine. Caution is advised with concomitant use of medicinal drugs which are known to lower the seizure threshold (such as tricyclic antidepressants or SSRIs, neuroleptics, phenothiazines or butyrophenone, mefloquine, chloroquine, bupropion or tramadol). (see section 4.4). In addition, caution is advised when stopping concomitant treatment with benzodiazepines due to potential withdrawal seizures.

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

Drugs that Affect Noradrenaline
Drugs that affect noradrenaline should be used cautiously when co-administered with atomoxetine because of the potential for additive or synergistic pharmacological effects. Examples include antidepressants such as imipramine, venlafaxine and mirtazapine, or the decongestants pseudoephedrine or phenylephrine.


Drugs that Affect Gastric pH
Drugs that elevate gastric pH (magnesium hydroxide/aluminium hydroxide, omeprazole) had no effect on atomoxetine bioavailability.

Drugs Highly Bound to Plasma Protein
In vitro drug-displacement studies were conducted with atomoxetine and other highly bound drugs at therapeutic concentrations. Warfarin, acetylsalicylic acid, phenytoin, or diazepam did not affect the binding of atomoxetine to human albumin. Similarly, atomoxetine did not affect the binding of these compounds to human albumin.