Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction
When other central depressant medicinal products (hypnotics/sedatives, analgesics, other psychiatric drugs, antihistamines), anesthetics or alcohol are used concomitantly, there may be reciprocal potentiation of the effects and adverse reactions (especially sedation and blood pressure lowering).
If patients on high neuroleptic doses undergo surgery, it is essential to carefully monitor for hypotension. The dose of the anesthetic or central depressant substances should be reduced in certain circumstances.
The concomitant administration of tricyclic antidepressants and fluphenazine leads to a rise in plasma antidepressant levels, and increased toxicity of both active substances (anticholinergic effect, lowering of seizure threshold, but above all cardiac effects [QT- interval prolongation]) needs to be anticipated. For this reason, this combination is not recommended.
The concomitant use of medicinal products that can also prolong the QT interval (e.g., class IA or III antiarrhythmics, macrolide antibiotics, antimalarials, antidepressants, other neuroleptics, antihistamines), result in hypokalemia or other electrolyte disturbances (e.g., certain diuretics) .or inhibit CYP2D6-mediated hepatic metabolism of fluphenazine (e.g., paroxetine, fluoxetine) should be avoided.
Combination with lithium salts can increase plasma fluphenazine levels. This increases the risk of extrapyramidal motor adverse reactions (gait disorders, hyperkinesia of the proximal parts of the body, tremor, rigidity, in isolated cases, brain damage that is difficult to reverse).
Conversely, the lithium plasma levels may also be increased. Severe neurotoxic syndromes have been reported very rarely with concomitant administration of neuroleptics and lithium.
When treatment with levodopa or dopamine agonists (e.g., bromocriptine, amantadine, cabergoline) is being given concomitantly, their effect may be attenuated.
With combined use of neuroleptics and other dopamine antagonists (e.g., metoclopramide, alizapride), the extrapyramidal motor effects may be more pronounced.
When fluphenazine is combined with medicinal products that also have an anticholinergic effect (e.g., antidepressants, atropine, biperiden), the anticholinergic effects may be additively increased. This can manifest as visual disturbances, an increase in intraocular pressure, dry mouth, an accelerated heart rate, constipation, problems with micturition, disorders of saliva secretion, speech block or memory disorders; the risk of drug-induced delirium is increased. The effect of fluphenazine may be simultaneously attenuated.
Combinations with sympathomimetics can result in hypertensive crises.
In patients on fluphenazine, hypotension should not be treated with epinephrine as epinephrine administration can lead to a further fall in blood pressure (“reverse epinephrine effect”). Norepinephrine (noradrenaline) may, however, be administered in severe shock states (see section 4.9).
Fluphenazine decanoate generally increases the hypotensive effect of antihypertensive drugs.
This may give rise to the increased occurrence of orthostatic circulatory dysregulation.
However, paradoxical reactions have also been described (guanethidine, clonidine, methyldopa).
The concomitant administration of monoamine oxidase (MAO) inhibitors can lead to a (further) fall in blood pressure and extrapyramidal motor effects.
The concomitant use of reserpine-containing products is not advised.
Respiratory depression caused by polypeptide antibiotics (e.g., colistin, polymyxin B) can be exacerbated by fluphenazine.
The effect of anticoagulants may be increased. For this reason, regular monitoring of the coagulation status is indicated at shorter intervals if anticoagulant therapy is being undertaken simultaneously.
The concomitant use of anticonvulsants, such as barbiturates or carbamazepine, can result in increased metabolism of fluphenazine.
The concomitant use of fluphenazine and phenytoin can lead to an alteration of phenytoin metabolism. This can give rise to toxic plasma levels in some circumstances.
Due to the fluphenazine-induced increase in prolactin, the response to gonadorelin administration may be reduced.
Fluphenazine decanoate should not be combined with clozapine as the risk of a blood disorder is potentially increased.
When fluphenazine decanoate and propranolol are used simultaneously, the plasma levels of both medicines are increased.
Concomitant treatment with piperazine-containing anthelmintics leads to an increased risk of extrapyramidal motor adverse reactions.
Clonidine can decrease the antipsychotic effect of fluphenazine.
When fluphenazine and cimetidine are used concomitantly, the plasma level of fluphenazine may be decreased.
Concomitant use of pentetrazol can trigger cerebral seizures.
Phenothiazines can increase the tendency to metrizamide-induced seizures. Fluphenazine should therefore not be given for at least 48 hours before and 24 hours after a myelogram.
The concomitant administration of fluphenazine with amphetamines or anorectics can result for antagonistic pharmacological reactions.
In individual cases, acute, severe, reversible parkinsonism have been reported by patients on combination therapy with a serotonin reuptake inhibitor and fluphenazine.
There is evidence that concomitant use of phenylalanine and neuroleptics increases the risk of the occurrence of tardive dyskinesia.
Patients receiving fluphenazine as treatment should avoid dehydroepiandrosterone replacement therapy as there have been cases reported where patients with elevated dehydroepiandrosterone levels did not respond to therapy with antipsychotics.
An increased risk of epileptic seizures has been described in schizophrenic patients who took products containing evening primrose oil while on treatment with phenothiazines.
Caffeine potentially counteracts the antipsychotic properties of phenothiazines. The data are, however, contradictory.
The metabolic control of insulin-requiring diabetics on phenothiazine treatment (especially with high doses) may become unstable and potentially require dietary and pharmacological measures or adjustment of antidiabetic therapy.
The result of a pregnancy test may be distorted (false-positive result) during treatment with fluphenazine decanoate.
Note
The patient should be told not to take any other medicinal products, including those obtained without a prescription, without the knowledge of the attendant physician.