Chemical formula: C₁₅H₂₁F₃N₂O₂ Molecular mass: 318.34 g/mol PubChem compound: 3404
Fluvoxamine interacts in the following cases:
There have been reports of the following haemorrhagic disorders: gastrointestinal bleeding, gynaecological haemorrhage, and other cutaneous or mucous bleeding with SSRIs. Caution is advised in patients taking SSRIs particularly in elderly patients and in patients who concomitantly use drugs known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most TCAs, acetylsalicylic acid, NSAIDs) or drugs that increase risk of bleeding, as well as in patients with a history of bleeding and in those with predisposing conditions (e.g. thrombocytopenia or coagulation disorders).
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.
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.
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.
Patients suffering from hepatic insufficiency should start on a low dose and be carefully monitored. Treatment with fluvoxamine has rarely been associated with an increase in hepatic enzymes, generally accompanied by clinical symptoms. In such cases treatment should be discontinued.
Patients suffering from renal insufficiency should start on a low dose and be carefully monitored.
The serotonergic effect of fluvoxamine may be enhanced if given in combination with other serotonergic drugs (including sumatriptan and selective serotonin reuptake inhibitors-SSRIs). In these rare cases, the serotoninergic syndrome may be caused.
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.
As with other psychotropic drugs, patients should be advised to avoid alcohol use while taking fluvoxamine.
In patients on oral anticoagulants and fluvoxamine, the risk for haemorrhage may increase and these patients should therefore be closely monitored.
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.
Reproductive toxicity studies in animals have shown that Fluvoxamine impairs male and female fertility. The safety margin for this effect was not identified. The relevance of these findings to humans is unknown.
Animal data have shown that fluvoxamine may affect sperm quality. Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far.
Fluvoxamine should not be used in patients attempting to conceive unless the clinical condition of the patient requires treatment with fluvoxamine.
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.
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.
As plasma concentrations of propranolol are increased in combination with fluvoxamine, the propranolol dose may need to be lowered.
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.
Fluvoxamine should not be co-administered with terfenadine, astemizole or cisapride as plasma concentrations may be increased resulting in a higher risk for QT-prolongation/Torsade de Pointes.
Isolated cases of cardiac toxicity have been reported when fluvoxamine was combined with thioridazine.
When given with fluvoxamine, warfarin plasma concentrations were significantly increased and prothrombin times prolonged.
Mydriasis has been reported in association with SSRIs such as fluvoxamine. Therefore caution should be used when prescribing fluvoxamine in patients with raised intraocular pressure or those at risk of acute narrow-angle glaucoma.
Fluvoxamine should be used with caution in patients with a history of mania/hypomania. Fluvoxamine should be discontinued in any patient entering a manic phase.
There is limited clinical experience of concomitant administration of fluvoxamine and ECT therefore caution is advisable.
Although in animal studies fluvoxamine has no pro-convulsive properties, caution is recommended when the drug is administered to patients with a history of convulsive disorders. Fluvoxamine should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Treatment with fluvoxamine should be discontinued if seizures occur or if seizure frequency increases.
Epidemiological data have suggested that the use of Selective Serotonin Reuptake Inhibitors (SSRIs) in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur.
Reproduction toxicity studies in animals revealed treatment related increases in embryotoxicity (embryofetal death, fetal eye abnormalities). The relevance to humans is unknown. The safety margin for reproductive toxicity is unknown.
Fluvoxamine should not be used during pregnancy unless the clinical condition of the woman requires treatment with fluvoxamine.
Isolated cases of withdrawal symptoms in the newborn child have been described after the use of fluvoxamine at the end of pregnancy.
Some newborns experience feeding and/or respiratory difficulties, seizures, temperature instability, hypoglycaemia, tremor, abnormal muscle tone, jitteriness, cyanosis, irritability, lethargy, somnolence, vomiting, difficulty in sleeping and constant crying after third trimester exposure to SSRIs and may require prolonged hospitalization.
Fluvoxamine is excreted via human milk in small quantities. Therefore, the drug should not be used by women, who breast feed.
Reproductive toxicity studies in animals have shown that Fluvoxamine impairs male and female fertility. The safety margin for this effect was not identified. The relevance of these findings to humans is unknown.
Animal data have shown that fluvoxamine may affect sperm quality. Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far.
Fluvoxamine should not be used in patients attempting to conceive unless the clinical condition of the patient requires treatment with fluvoxamine.
Fluvoxamine up to 150 mg has no or negligible influence on the ability to drive and use machines. It showed no effect on psychomotor skills associated with driving and operating machinery in healthy volunteers. However, somnolence has been reported during treatment with fluvoxamine. Therefore, caution is recommended until the individual response to the drug has been determined.
Adverse events, observed in clinical studies at frequencies listed below, are often associated with the illness and are not necessarily related to treatment.
Frequency estimate: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Frequency not known: Hyperprolactinemia, inappropriate antidiuretic hormone secretion
Common: Anorexia
Frequency not known: Hyponatraemia, weight increased, weight decreased
Uncommon: Hallucination, confusional stage, aggression
Rare: Mania
Frequency not known: Suicidal ideation
Common: Agitation, nervousness, anxiety, insomnia, somnolence, tremor, headache, dizziness
Uncommon: Extrapyramidal disorder, ataxia
Rare: Convulsion
Frequency not known: Serotonin syndrome, neuroleptic malignant syndrome-like events, paresthesia, dysgeusia, and SIADH have been reported. Psychomotor restlessness/akathisia.
Frequency not known: Glaucoma, Mydriasis
Frequency not known: Micturition disorder (including urinary retention, urinary incontinence, pollakiuria, nocturia and enuresis)
Common: Palpitations/tachycardia
Uncommon: (Orthostatic) hypotension
Frequency not known: Haemorrhage (e.g. gastrointestinal haemorrhage, gynaecological, haemorrhage, ecchymosis, purpura)
Common: Abdominal pain, constipation, diarrhoea, dry mouth, dyspepsia, nausea, vomiting
Rare: Hepatic function abnormal
Common: Hyperhydrosis, Sweating
Uncommon: Cutaneous hypersensitivity reactions (incl. angioneurotic oedema, rash, pruritis)
Rare: Photosensitivity reaction
Uncommon: Arthralgia, myalgia
Frequency not known: **Bone fractures
Uncommon: Abnormal (delayed) ejaculation
Rare: Galactorrhoea
Frequency not known: Anorgasmia, menstrual disorders (such as amenorrhea, hypomenorrhea, metrorrhagia, menorrhagia)
Common: Asthenia, malaise
Frequency not known: Drug withdrawal syndrome including drug withdrawal syndrome neonatal
* Nausea, sometimes accompanied by vomiting is the most frequently observed symptom associated with fluvoxamine treatment. This side effect usually diminishes within the first two weeks of treatment.
** Class effects: Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs). The mechanism leading to this risk is unknown.
Cases of suicidal ideation and suicidal behaviours have been reported during fluvoxamine therapy or early after treatment discontinuation.
Discontinuation of fluvoxamine (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbance (including paraesthesia, visual disturbance and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation and anxiety, irritability, confusion, emotional instability, nausea and/or vomiting, diarrhoea, sweating, palpitations, headache and tremor are the most commonly reported reactions. Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when fluvoxamine treatment is no longer required, gradual discontinuation by dose tapering should be carried out.
In one 10-week placebo-controlled trial in children and adolescents with OCD, frequently reported adverse events with a higher incidence than placebo, were: insomnia, asthenia, agitation, hyperkinesia, somnolence and dyspepsia. Serious adverse events in this study included: agitation and hypomania.
Convulsions in children and adolescents have been reported during use outside clinical trials.
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