Drug Interaction Report

MONITOR: Coadministration with methylphenidate may increase the plasma concentrations and effects of selective serotonin reuptake inhibitors (SSRIs). Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some antidepressants including SSRIs. There have been isolated reports of adverse reactions such as hallucinations, confusion, seizures, and serotonin syndrome during concomitant use of methylphenidate with an SSRI, which resolved following discontinuation of one or both drugs. Nevertheless, the combination has been used therapeutically to improve clinical response in the treatment of attention-deficit hyperactivity disorder and to augment the effects of SSRIs in the treatment of depression.

MANAGEMENT: Pharmacologic response to SSRIs should be monitored more closely whenever methylphenidate (racemic) or dexmethylphenidate (the more pharmacologically active d-enantiomer) is added to or withdrawn from therapy, and the dosage of one or both drugs adjusted as necessary.

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MONITOR: Coadministration with fluoxetine may increase the plasma concentrations of certain neuroleptic agents and potentiate the risk of extrapyramidal adverse effects. The proposed mechanism is inhibition of CYP450 2D6 metabolism by fluoxetine and its active metabolite, norfluoxetine. In 10 psychiatric patients stabilized on risperidone therapy (4 to 6 mg/day), the addition of fluoxetine (20 mg/day) led to a mean 4-fold increase in plasma risperidone concentrations and a 75% increase in levels of active moiety (i.e. sum of the concentrations of risperidone and its active 9-hydroxy metabolite). One patient developed severe akathisia and two developed Parkinsonian symptoms within the first two weeks. In contrast, mean plasma concentrations of haloperidol were elevated by just 20% following the addition of fluoxetine (20 mg/day for 7 to 10 days) in eight psychotic patients stabilized on haloperidol, and extrapyramidal side effects did not increase appreciably. However, haloperidol has been implicated clinically in various case reports, as has the phenothiazine fluphenazine. Some believe that a pharmacodynamic interaction may be partially responsible, as fluoxetine alone has been associated with extrapyramidal symptoms, possibly due to serotonergic inhibition of nigrostriatal dopaminergic pathways.

MANAGEMENT: Caution is recommended if fluoxetine is prescribed with phenothiazines or other neuroleptic agents that are thought to be metabolized by CYP450 2D6. Plasma neuroleptic levels and pharmacologic effects should be closely monitored and the dosage(s) adjusted accordingly, particularly following initiation or discontinuation of fluoxetine in patients who are stabilized on their neuroleptic regimen. Patients should be advised to contact their physician if they develop extrapyramidal symptoms such as tremor, shuffling gait, drooling, a mask-like face, tongue stiffness, muscle spasms or rigidity, and involuntary movements. Due to the long half-life of fluoxetine and norfluoxetine, the risk of an interaction may exist for an extended period (up to several weeks) after discontinuation of fluoxetine.

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MONITOR: The coadministration of risperidone with serdexmethylphenidate, dexmethylphenidate, or methylphenidate, when there is an increase or decrease of dosage of either medication, may increase the risk of extrapyramidal symptoms. The mechanism of this interaction has not been delineated.

MANAGEMENT: Caution is advised if risperidone must be used concomitantly with methylphenidate, dexmethylphenidate, or serdexmethylphenidate. Patients should be monitored more closely whenever either drug is added to or withdrawn from therapy and whenever either dosage is changed. Patients should be monitored for the development of extrapyramidal symptoms (e.g., tremor, shuffling gait, drooling, mask-like face, tongue stiffness, muscle spasms or rigidity, involuntary movements) and changes in mental status.

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GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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GENERALLY AVOID: Alcohol may exacerbate the adverse central nervous system effects of psychoactive drugs, including methylphenidate.

GENERALLY AVOID: Consumption of alcohol while taking certain sustained-release formulations of methylphenidate may cause rapid release of the drug, resulting in increased systemic levels of methylphenidate. In vitro studies have been conducted using Metadate CD 60 mg and Ritalin LA 40 mg capsules, as well as Concerta 18 mg tablet. At an alcohol concentration of 40%, an increase in the release rate of methylphenidate was observed in the first hour for Metadate CD and Ritalin LA, resulting in 84% and 98% of the methylphenidate being released, respectively. In contrast, there was no increased release of methylphenidate in the first hour for Concerta. These results are considered to be representative of the other available strengths of the corresponding product.

MANAGEMENT: Patients treated with methylphenidate should be advised to avoid alcohol or medications that contain alcohol.

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GENERALLY AVOID: Risperidone oral solution is not compatible with either tea or cola. In addition, alcohol may potentiate some of the pharmacologic effects of risperidone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Risperidone oral solution should not be mixed with tea or cola. It may be taken with water, coffee, orange juice, or lowfat milk. Patients should also be advised to avoid consumption of alcohol.

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