Chemical formula: C₁₉H₂₂ClN₅O Molecular mass: 371.864 g/mol PubChem compound: 5533
Trazodone interacts in the following cases:
Concomitant use of trazodone hydrochloride with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Caution should be used when these drugs are co-administered with trazodone hydrochloride.
Possible interactions with monoamine oxidase inhibitors have occasionally been reported. Although some clinicians do give both concurrently, use of trazodone hydrochloride with MAOIs, or within two weeks of stopping treatment with these compounds is not recommended. The giving of MAOIs within one week of stopping trazodone hydrochloride is also not recommended.
Undesirable effects may be more frequent when trazodone hydrochloride is administered together with preparations containing Hypericum perforatum (St John’s Wort).
Severe orthostatic hypotension has been observed in case of concomitant use of phenothiazines, like e.g. chlorpromazine, fluphenazine, levomepromazine, perphenazine.
Concurrent administration of trazodone with tricyclic antidepressants should be avoided due to the risk of interaction. Serotonin syndrome and cardiovascular side effects are possible.
Trazodone hydrochloride intensifies the sedative effects of alcohol. Alcohol should be avoided during trazodone hydrochloride therapy.
In vitro drug metabolism studies suggest that there is a potential for drug interactions when trazodone hydrochloride is given with potent CYP3A4 inhibitors such as erythromycin, ketoconazole, itraconazole, ritonavir, indinavir, and nefazodone. It is likely that potent CYP3A4 inhibitors may lead to substantial increases in trazodone plasma concentrations with the potential for adverse effects. Exposure to ritonavir during initiation or resumption of treatment in patients receiving trazodone hydrochloride will increase the potential for excessive sedation, cardiovascular, and gastrointestinal effects. It has been confirmed in in-vivo-studies in healthy volunteers, that a ritonavir dose of 200 mg BID increased the plasma levels of trazodone hydrochloride by greater than two-fold, leading to nausea, syncope and hypotension.
If trazodone hydrochloride is used with a potent CYP3A4 inhibitor, a lower dose of trazodone hydrochloride should be considered. However, the co-administration of trazodone hydrochloride and potent CYP3A4 inhibitors should be avoided where possible.
Trazodone hydrochloride may enhance the effects of muscle relaxants and volatile anaesthetics, and caution should be exercised in such instances.
Carbamazepine reduced plasma concentrations of trazodone when co-administered. Concomitant use of carbamazepine 400 mg daily led to a decrease of plasma concentrations of trazodone hydrochloride and its active metabolite m-chlorophenylpiperazine of 76% and 60%, respectively. Patients should be closely monitored to see if there is a need for an increased dose of trazodone hydrochloride when taken with carbamazepine.
The metabolism of antidepressants is inhibited by cimetidine and some other antipsychotics.
Studies in laboratory animals suggest that Trazodone hydrochloride may inhibit most of the acute actions of clonidine.
Concurrent use with trazodone hydrochloride may result in elevated serum levels of digoxin or phenytoin. Monitoring of serum levels should be considered in these patients.
Rare cases have been reported of elevated trazodone hydrochloride plasma levels and adverse effects when trazodone hydrochloride had been combined with fluoxetine, a CYP1A2/2D6 inhibitor. The mechanism underlying a pharmacokinetic interaction is not fully understood. A pharmacodynamic interaction (serotonin syndrome) could not be excluded.
Trazodone hydrochloride has been well tolerated in depressed schizophrenic patients receiving standard phenothiazine therapy and also in depressed parkinsonian patients receiving therapy with levodopa. Antidepressants can accelerate the metabolism of levodopa.
There have been reports of changes in prothrombin time in patients concomitantly receiving trazodone and warfarin.
Data on a limited number (<200) of exposed pregnancies indicate no adverse effects of trazodone on pregnancy or on the health of the foetus/newborn child. To date, no other relevant epidemiological data are available. The safety of trazodone in human pregnancy has not been established. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development at therapeutic doses. On basic principles, therefore, its use during the first trimester should be avoided.
Caution should be exercised when prescribing to pregnant women. When trazodone is used until delivery, newborns should be monitored for the occurrence of withdrawal symptoms.
Limited data indicate that excretion of Trazodone in human breast milk is low, but levels of the active metabolite are not known. Due to the paucity of data, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with trazodone should be made taking into account the benefit of breast-feeding to the child and the benefit of trazodone therapy to the woman.
The effect on human fertility has not been evaluated.
Trazodone has minor or moderate influence on the ability to drive and use machines. As with all other drugs acting on the central nervous system, patients should be cautioned against the risks of driving or operating machinery until they are sure they are not affected by drowsiness, sedation, dizziness, confusional states, or blurred vision.
Cases of suicidal ideation and suicidal behaviours have been reported during Trazodone hydrochloride therapy or early after treatment discontinuation.
Trazodone hydrochloride has had no effect on arterial blood pCO2 or pO2 levels in patients with severe respiratory insufficiency due to chronic bronchial or pulmonary disease.
The following symptoms, some of which are commonly reported in cases of untreated depression, have also been recorded in patients receiving Trazodone hydrochloride therapy.
Frequency not known (cannot be estimated from the available data)
Frequency not known: Blood dyscrasias (including agranulocytosis, thrombocytopenia, eosinophilia, leucopenia and anaemia)
Frequency not known: Allergic reactions
Frequency not known: Syndrome of Inappropriate Antidiuretic Hormone Secretion
Frequency not known: Hyponatraemia1, weight loss, anorexia, increased appetite
Frequency not known: Suicidal ideation or suicidal behaviours, confusional state, insomnia, disorientation, mania, anxiety, nervousness, agitation (very occasionally exacerbating to delirium), delusion, aggressive reaction, hallucinations, nightmares, libido decreased, withdrawal syndrome
Frequency not known: Serotonin syndrome, convulsion, neuroleptic malignant syndrome, dizziness, vertigo, headache, drowsiness2, restlessness, decreased alertness, tremor, blurred vision, memory disturbance, myoclonus, expressive aphasia, paraesthesia, dystonia, taste altered
Frequency not known: Cardiac arrhythmias3 (including Torsade de Pointes, palpitations, premature ventricular contractions, ventricular couplets, ventricular tachycardia), bradycardia, tachycardia, ECG abnormalities (QT prolongation)
Frequency not known: Orthostatic hypotension, hypertension, syncope
Frequency not known: Nasal congestion, dyspnoea
Frequency not known: Nausea, vomiting, dry mouth, constipation, diarrhoea, dyspepsia, stomach pain, gastroenteritis, increased salivation, paralytic ileus
Frequency not known: Hepatic function abnormalities (including jaundice and hepatocellular damage)4, cholestasis intrahepatic, severe hepatic disorders such as hepatitis/fulminant hepatitis, hepatic failure with potential fatal outcome.
Frequency not known: Skin rash, pruritus, hyperhidrosis
Frequency not known: Pain in limb, back pain, myalgia, arthralgia
Frequency not known: Micturition disorder
Frequency not known: Priapism
Frequency not known: Weakness, oedema, influenza-like symptoms, fatigue, chest pain, fever
Frequency not known: Elevated liver enzymes
1 Fluid and electrolyte status should be monitored in symptomatic patients.
2 Trazodone is a sedative antidepressant and drowsiness, sometimes experienced during the first days of treatment, usually disappears on continued therapy.
3 Studies in animals have shown that trazodone is less cardiotoxic than the tricyclic antidepressants, and clinical studies suggest that the drug may be less likely to cause cardiac arrhythmias in man. Clinical studies in patients with pre-existing cardiac disease indicate that trazodone may be arrhythmogenic in some patients in that population.
4 Adverse effects on hepatic function, sometimes severe, have been rarely reported. Should such effects occur, trazodone should be immediately discontinued.
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