Interactions : אינטראקציות

4.5   Interactions with other medicinal products and other forms of interaction
Pharmacodynamic interactions

The serotonergic effects of fluvoxamine may be enhanced when used in combination with other serotonergic agents (including tramadol, buprenorphine, buprenorphine/naloxone, triptans, linezolid, SSRIs and St. John's Wort preparations) and may result in a potentially life-threatening condition.. (See also section 4.4).
Fluvoxamine has been used in combination with lithium in the treatment of severely ill, drug-resistant patients. However, lithium (and possibly also tryptophan) enhances the serotonergic effects of fluvoxamine. The combination should be used with caution in patients with severe, drug-resistant depression.
In patients on oral anticoagulants and fluvoxamine, the risk for haemorrhage may increase and these patients should therefore be closely monitored.
As with other psychotropic drugs patients should be advised to avoid alcohol use while taking fluvoxamine.

Monoamine oxidase inhibitors

Fluvoxamine should not be used in combination with MAOIs, including linezolid, due to risk of serotonin syndrome (see also section 4.3 and 4.4).
Effect of fluvoxamine on the oxidative metabolism of other drugs 
Fluvoxamine can inhibit the metabolism of drugs metabolized by certain cytochrome P450 isoenzymes (CYPs). A strong inhibition of CYP1A2 and CYP 2C19 is demonstrated in in vitro and in vivo studies. CYP2C9, CYP 2D6 and CYP3A4 are inhibited to a lesser extent. Drugs which are largely metabolised via these isoenzymes are eliminated slower and may have higher plasma concentrations when co-administered with fluvoxamine.

In case of prodrugs which are activated by CYPs mentioned above, like clopidogrel, plasma concentrations of the active substance/metabolite may be lower when co- administered with fluvoxamine. As a precaution concomitant use of clopidogrel and fluvoxamine should be discouraged.

Concomitant therapy of fluvoxamine and these drugs should be initiated at or adjusted to the low end of their dose range. Plasma concentrations, effects or adverse effects of co-administered drugs should be monitored and their dosage should be reduced, if necessary. This is particularly relevant for drugs with a narrow therapeutic index.

Compounds with narrow therapeutic index

Co-administration with fluvoxamine and drugs with a narrow therapeutic index (such as tacrine, theophylline, methadone, mexiletine, phenytoin, carbamazepine and cyclosporine) should be carefully monitored when these drugs are metabolized exclusively or by a combination of CYPs inhibited by fluvoxamine.

If necessary, dose adjustment of these drugs is recommended.

Due to the narrow therapeutic index of pimozide and its known ability to prolong QT interval, concomitant use of pimozide and fluvoxamine is contraindicated - see section 4.3.

An increase in previously stable plasma levels of those tricyclic antidepressants (e.g.
clomipramine, imipramine, amitriptyline) and neuroleptics (e.g. clozapine and olanzapine, quetiapine) which are largely metabolised through cytochrome P450 1A2 when given together with fluvoxamine, has been reported. A decrease in the dose of these products should be considered if treatment with fluvoxamine is initiated.

The plasma levels of oxidatively metabolised benzodiazepines (e.g. triazolam, midazolam, alprazolam, and diazepam) are likely to be increased when co- administered with fluvoxamine. The dosage of these benzodiazepines should be reduced during co-administration with fluvoxamine.

As plasma concentrations of ropinirole may be increased in combination with fluvoxamine thus increasing the risk of overdose, surveillance and reduction in the dosage of ropinirole during fluvoxamine treatment and after its withdrawal may be required.

As plasma concentrations of propranolol are increased in combination with fluvoxamine, the propranolol dose may need to be lowered.

When given with fluvoxamine, warfarin plasma concentrations were significantly increased and prothrombin times prolonged.
Cases of increased side effects

Isolated cases of cardiac toxicity have been reported when fluvoxamine was combined with thioridazine.

Caffeine plasma levels are likely to be increased during co-administration with fluvoxamine. Thus, patients who consume high quantities of caffeine containing beverages should lower their intake when fluvoxamine is administered and adverse caffeine effects (like tremor, palpitations, nausea, restlessness, insomnia) are observed.

Terfenadine, astemizole, cisapride, sildenafil (see also section 4.4).

Fluvoxamine does not influence plasma concentrations of digoxin.
Fluvoxamine does not influence plasma concentrations of atenolol.