Drug Interaction Report

FluvoxaMINE may significantly increase the blood levels of OLANZapine. You may be more likely to experience side effects such as dizziness; drowsiness; dry mouth; constipation; increased appetite; weight gain; increased blood sugar and cholesterol or triglyceride levels; cognitive and motor impairment; involuntary muscle movements involving the face, tongue, or other parts of the body; difficulty swallowing; low blood pressure (especially at the start of treatment or after a dose increase); blood pressure increases; priapism (prolonged and painful erection unrelated to sexual activity); irregular heart rhythm; and seizures. Let your doctor know if your condition changes or you experience increased side effects. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

FluvoxaMINE may increase the blood levels of QUEtiapine in some patients. This may increase the risk and/or severity of side effects such as dizziness; drowsiness; dry mouth; constipation; increased appetite; weight gain; increased blood sugar and cholesterol or triglyceride levels; cognitive and motor impairment; involuntary muscle movements involving the face, tongue, or other parts of the body; difficulty swallowing; low blood pressure (especially at the start of treatment or after a dose increase); blood pressure increases (reported in children and teenagers); irregular heart rhythm; and seizures. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

OLANZapine may interfere with blood glucose control and reduce the effectiveness of metFORMIN and other diabetic medications. Monitor your blood sugar levels closely. You may need a dose adjustment of your diabetic medications during and after treatment with OLANZapine. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

QUEtiapine may interfere with blood glucose control and reduce the effectiveness of metFORMIN and other diabetic medications. Monitor your blood sugar levels closely. You may need a dose adjustment of your diabetic medications during and after treatment with QUEtiapine. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: There is some concern that quetiapine may have additive cardiovascular effects in combination with other drugs that are known to prolong the QT interval of the electrocardiogram. In clinical trials, quetiapine was not associated with a persistent increase in QT intervals, and there was no statistically significant difference between quetiapine and placebo in the proportions of patients experiencing potentially important changes in ECG parameters including QT, QTc, and PR intervals. However, QT prolongation and torsade de pointes have been reported during post marketing use in cases of quetiapine overdose and in patients with risk factors such as underlying illness or concomitant use of drugs known to cause electrolyte imbalance or increase QT interval. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, certain agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants) may have additive parasympatholytic and central nervous system-depressant effects when used in combination with quetiapine. Excessive parasympatholytic effects may include paralytic ileus, hyperthermia, mydriasis, blurred vision, tachycardia, urinary retention, psychosis, and seizures.

MONITOR: Coadministration of quetiapine with drugs that possess serotonergic activity (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), etc.) may increase the risk of serotonin syndrome, a rare but serious and potentially fatal condition. Combining quetiapine with other serotonergic drugs may increase the risk of serotonin syndrome by relatively enhancing 5-HT1A receptor activity. However, data are currently limited to case reports. In one case report, an 85-year-old woman developed serotonin syndrome within hours of increasing quetiapine from 12.5 mg to 25 mg/day while also taking escitalopram, mirtazapine, sulpiride, and olanzapine; symptoms resolved within 48 hours after the discontinuation of all serotonergic medications. Symptoms of serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Coadministration of quetiapine with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use of quetiapine with other agents that both prolong the QT interval and possess or enhance serotonergic activity is required. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Patients should also be monitored closely for, and counseled about the signs and symptoms of serotonin syndrome (e.g., altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor), especially during initiation and dose escalations. Due to variability and occasionally prolonged half-lives of these coadministered agents, consulting individual product labeling for specific guidance is advised.

MetFORMIN should be taken with meals, and excessive alcohol intake (either short-term binge drinking or frequent consumption) should be avoided during treatment. Taking metFORMIN with alcohol may increase the risk of a rare but serious and potentially life-threatening condition known as lactic acidosis, which is a buildup of lactic acid in the blood that can occasionally occur during treatment with metformin-containing products. Lactic acidosis is more likely to occur if you have kidney or liver disease, acute or unstable congestive heart failure, or dehydration. You should seek immediate medical attention if you develop potential signs and symptoms of lactic acidosis such as fatigue, weakness, muscle pain, increasing drowsiness, abdominal pain or discomfort, slow or irregular heartbeat, breathing difficulty, chills, and other unusual symptoms. Alcohol may also affect blood glucose levels in patients with diabetes. Both hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar) may occur, depending on how much and how often you drink. You should avoid using alcohol if your diabetes is not well controlled or if you have high triglycerides, neuropathy (nerve damage), or pancreatitis. Moderate alcohol consumption generally does not affect blood glucose levels if your diabetes is under control. However, you should limit your alcohol intake due to the risk of lactic acidosis with metformin. Avoid drinking alcohol on an empty stomach or following exercise, as it may increase the risk of hypoglycemia. Talk to your doctor or pharmacist if you have any questions or concerns about metformin.

Alcohol can increase the nervous system side effects of fluvoxaMINE such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with fluvoxaMINE. Do not use more than the recommended dose of fluvoxaMINE, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

Alcohol can increase the nervous system side effects of OLANZapine such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with OLANZapine. Do not use more than the recommended dose of OLANZapine, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit juice and/or grapefruit may increase the plasma concentrations of quetiapine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. For example, in 12 healthy volunteers, administration of a single 25 mg dose of quetiapine with the potent CYP450 3A4 inhibitor ketoconazole (200 mg once daily for 4 days) increased mean quetiapine peak plasma concentration (Cmax) and systemic exposure (AUC) by 3.4- and 6.2-fold, respectively, and decreased mean oral clearance by 84%. In general, the effects of grapefruit products are concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. High plasma levels of quetiapine may increase the risk and/or severity of serious adverse effects such as extrapyramidal symptoms, tardive dyskinesia, hyperglycemia, dyslipidemia, hyperprolactinemia, orthostatic hypotension, blood pressure increases (in children and adolescents), priapism, QT prolongation, cognitive and motor impairment, dysphagia, heat-related illnesses due to disruption of body temperature regulation, and symptoms of serotonin syndrome (e.g., mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea).

Food may have varying effects on the absorption of quetiapine from immediate-release versus prolonged-release formulations. In a study examining the effects of food on the bioavailability of quetiapine, a high-fat meal was found to produce statistically significant increases in the quetiapine prolonged release Cmax and AUC of approximately 50% and 20%, respectively. It cannot be excluded that the effect of a high fat meal on the formulation may be larger. In comparison, a light meal had no significant effect on the Cmax or AUC of quetiapine.

Quetiapine may potentiate the cognitive and motor effects of alcohol. The mechanism is likely related to the primary central nervous system effects of quetiapine.

MANAGEMENT: According to the manufacturer, consumption of grapefruit juice should be avoided during treatment with quetiapine. Quetiapine immediate-release tablets may be taken with or without food. It is recommended that quetiapine prolonged release is taken once daily without food or with a light meal. Consumption of alcohol should be limited and used with caution while taking quetiapine.

The recommended maximum number of medicines in the 'antipsychotics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antipsychotics' category:

• Seroquel XR (quetiapine)
• Zyprexa (olanzapine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.