Fluoxetine arrhythmia with

Evidence is limited, however the interaction is potentially severe as raised pimozide levels can cause torsade de pointes arrhythmias, which can be fatal. The manufacturers of pimozide contraindicate its use with SSRIs, and in the UK they specifically name sertraline, paroxetine, and citalo-pram which has been seen to cause QT prolongation with pimozide, and its isomer, escitalopram. The US manufacturers additionally contraindicate fluvoxamine." Neither manufacturer mentions fluoxetine (except with regard to the possibility of additive bradycardia"), but as it is known to have greater effects on CYP2D6 than either sertraline or citalopram, it would seem prudent to also consider it as contraindicated. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Newer antidepressants (eg, fluoxetine, paroxetine, citalopram, venlafaxine) are mostly SSRIs and are generally safer than the tricyclic antidepressants and monoamine oxidase inhibitors, although they can cause seizures. Bupropion (not an SSRI) has caused seizures even in therapeutic doses. Some antidepressants have been associated with QT prolongation and torsade de pointes arrhythmia. SSRIs may interact with each other or especially with monoamine oxidase inhibitors to cause the serotonin syndrome, characterized by agitation, muscle hyperactivity, and hyperthermia (see Chapter 16). 

Adverse affects Commonly observed adverse effects of fluoxetine are summarized in Figure 12.7. Loss of libido, delayed ejaculation and anorgasmia are probably under-reported side effects often noted by clinicians but are not prominently featured in the list of standard side effects. Overdoses of fluoxetine do not cause cardiac arrhythmias but can cause seizures. For example, in a report of patients who took an overdose of fluoxetine (up to 1200 mg compared with 20 mg/day as a therapeutic dose) about half of the patients had no symptoms. 

Abebe-Campino G, Offer D, Stahl B, Merlob P. Cardiac arrhythmia in a newborn infant associated with fluoxetine use during pregnancy. Ann Pharmacother... 

SSRIs TERFENADINE Possibility oft plasma concentrations of these drugs and potential risk of dangerous arrhythmias These drugs are metabolized mainly by CYP3A4. Fluvoxamine and fluoxetine are inhibitors of CYP3A4 but are relatively weak compared with ketoconazole, which is possibly 100 times more potent as an inhibitor The interaction is unlikely to be of clinical significance but need to be aware... 

ARTEMETHER WITH LUMEFANTRINE SSRIs This antimalarial may cause dose-related dangerous arrhythmias A substrate mainly of CYP3A4, which may be inhibited by high doses of fluvoxamine and to a lesser degree by fluoxetine Manufacturers recommend avoidance of antidepressants... 

Broom 2. Ginkgo biloba 3. Scopolia 4. Yohimbine 1. TCAs (e.g. amitriptyline, nortriptyline, clomipramine) 2. SSRIs (e.g. fluvoxamine fluoxetine, paroxetine) 3. Venlafaxine 4. Trazodone May develop cardiac arrhythmias and side-effects such as dryness of the mouth, retention of urine and tachycardia, t sedation Broom contains cardioactive alkalamines such as sparteine Inhibits metabolizing enzymes Anticholinergic properties (hyoscine present in scopolia may worsen side-effects of TCAs-additive antimuscarinic effects) Yohimbine alone can cause hypertension, but lower doses cause hypertension when combined with TCAs Unknown mechanism (ginkgo t sedative effects of trazodone) St John s wort inhibits the uptake of serotonin and thereby t serotonin levels Avoid concomitant use. An SSRI may be a better alternative to be used with broom... 

Use with CYP450 3A4 inhibitors (e.g., drugs such as fluoxetine, sertraline, fluvoxamine, and nefazodone foods such as grapefruit juice) can raise pimozide levels and increase the risks of dangerous arrhythmias... 

A patient who had been taking astemizole 10 mg daily for 10 months with fluoxetine, alprazolam, isradipine, and diuretics with potassium had a syncopal episode one hour after taking the first dose of quinine sulphate 260 mg for leg cramp. The ECG showed recurrent episodes of torsade de pointes with a QT interval of greater than 680 milliseconds. The only electrolyte abnormality was slight hypomagnesaemia. Intravenous magnesium was given and the patient s QT interval shortened to 420 milliseconds over 3 days. The manufacturers have on record two other case reports of cardiac arrhythmias possibly attributable to an interaction between astemizole and quinine. 

Pimozide levels are expected to rise when used with fluoxetine, fluvoxamine, paroxetine, or sertraline, which would increase the risk of potentially fatal torsade de pointes arrhythmias. The use of SSRIs and pimozide has also led to extrapyramidal adverse effects, oculogyric crises and sedation in rare cases. 

The manufacturers of sertindole contraindicate the concurrent use of cimetidine, diltiazem, erythromycin, itraconazole, ketoco-nazole, terfenadine and verapamil because of an increased risk of cardiac arrhythmias. Carbamazepine and phenytoin reduce plasma sertindole levels whereas fluoxetine and paroxetine increase them. No clinically relevant interactions occur with alprazolam, antacids, food or tobacco smoking. 

US manufacturer of fluoxetine contraindicates its use with thioridazine due to the risk of ventricular arrhythmias. 

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