Drug Interaction Report

Using mirtazapine together with OXcarbazepine may increase side effects such as dizziness, drowsiness, confusion, and difficulty concentrating. Some people, especially the elderly, may also experience impairment in thinking, judgment, and motor coordination. You should avoid or limit the use of alcohol while being treated with these medications. Also avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medications affect you. Talk to your doctor if you have any questions or concerns. 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.

Alcohol can increase the nervous system side effects of mirtazapine 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 mirtazapine. Do not use more than the recommended dose of mirtazapine, 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 OXcarbazepine 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 OXcarbazepine. Do not use more than the recommended dose of OXcarbazepine, 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.

A major depressive episode can be the initial presentation of bipolar disorder. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment with a tetracyclic antidepressant. This screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that tetracyclic antidepressants are not approved for use in bipolar depression.

The use of tetracyclic antidepressants (TCAs) has occasionally been associated with significant orthostatic hypotension secondary to the alpha-1 adrenergic blocking effects of these drugs. Therapy with TCAs should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with TCAs. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

The use of tetracyclic antidepressants (TCAs) has occasionally been associated with significant orthostatic hypotension secondary to the alpha-1 adrenergic blocking effects of these drugs. Therapy with TCAs should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with TCAs. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Antiepileptic drugs can increase depression and suicidal thoughts or behaviors in patients receiving these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts and unusual changes in mood or behavior. Caregivers and family should be alert for the emergence or worsening of symptoms. Behaviors of concern should be reported immediately to the healthcare providers.

A major depressive episode can be the initial presentation of bipolar disorder. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment with a tetracyclic antidepressant. This screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that tetracyclic antidepressants are not approved for use in bipolar depression.

Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Families and caregivers should be advised of the need for close observation and communication with the treating physician. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to these patients.

The use of tetracyclic antidepressants (TCAs) has occasionally been associated with significant orthostatic hypotension secondary to the alpha-1 adrenergic blocking effects of these drugs. Therapy with TCAs should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with TCAs. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

The use of tetracyclic antidepressants (TCAs) has occasionally been associated with significant orthostatic hypotension secondary to the alpha-1 adrenergic blocking effects of these drugs. Therapy with TCAs should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with TCAs. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

The use of tetracyclic antidepressants (TCAs) has occasionally been associated with significant orthostatic hypotension secondary to the alpha-1 adrenergic blocking effects of these drugs. Therapy with TCAs should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with TCAs. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

The use of tetracyclic antidepressants (TCAs) has occasionally been associated with significant orthostatic hypotension secondary to the alpha-1 adrenergic blocking effects of these drugs. Therapy with TCAs should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with TCAs. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

The use of tetracyclic antidepressants (TCAs) has occasionally been associated with significant orthostatic hypotension secondary to the alpha-1 adrenergic blocking effects of these drugs. Therapy with TCAs should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with TCAs. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Most anticonvulsants are primarily metabolized by the liver. Metabolic activity may be decreased in patients with liver disease, resulting in elevated drug levels and increased risk of toxicity. Therapy with anticonvulsants should be administered cautiously in patients with mild and moderate liver impairment. Therapy with these drugs is mostly not recommended in patients with severe liver impairment. Caution is also advised when treating patients with a history of liver disease, since the use of some anticonvulsants has been associated with hepatotoxicity. Baseline and periodic evaluation of liver function is recommended. Therapy should be discontinued and not readministered if evidence of liver damage is observed and felt to be drug-related.

Mirtazapine is extensively metabolized by the liver. Both the parent drug and metabolites, some of which are pharmacologically active, are excreted by the kidney. The clearance of mirtazapine has been shown to decrease in patients with moderate to severe renal or hepatic impairment. Therapy with mirtazapine should be administered cautiously in such patients. Dosage adjustments may be necessary.

The use of tetracyclic antidepressants has been associated with neutropenia (ANC < 500/mm3) and agranulocytosis (ANC < 500/mm3) with associated signs and symptoms,( e.g., fever, infection, etc.). Patients with preexisting neutropenia or agranulocytosis should be monitored closely during therapy for further decreases in white blood cell (WBC) counts. Treatment should be discontinued in any patient who develops a sore throat, fever, stomatitis, or other signs of infection along with a low WBC count.

Tricyclic and tetracyclic antidepressants (TCAs) may potentiate the effects of circulating catecholamines. Enhanced sympathetic activity can provoke hypertensive crises in patients with pheochromocytoma or other tumors of the adrenal medulla, such as some neuroblastomas. Therapy with TCAs should be administered cautiously in patients with these tumors.

Mirtazapine is extensively metabolized by the liver. Both the parent drug and metabolites, some of which are pharmacologically active, are excreted by the kidney. The clearance of mirtazapine has been shown to decrease in patients with moderate to severe renal or hepatic impairment. Therapy with mirtazapine should be administered cautiously in such patients. Dosage adjustments may be necessary.

Most anticonvulsants are primarily excreted by the kidney. The plasma clearance may be decreased and the half-life prolonged in patients with impaired renal function. Therapy with anticonvulsants should be administered cautiously in patients with significant renal dysfunction. In most cases it is recommended to adjust the dosage in patients with CrCl <50 mL/min to half the usual starting dose and then increase slowly to achieve the desired clinical response. The renal function should be monitored regularly in patients receiving therapy.

The use of tetracyclic antidepressants (TCAs) has occasionally been associated with significant orthostatic hypotension secondary to the alpha-1 adrenergic blocking effects of these drugs. Therapy with TCAs should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with TCAs. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Some anticonvulsants can cause clinically significant hyponatremia (Na < 125 mmol/L). Therapy with these drugs should be administered cautiously in patients with conditions predisposing to hyponatremia, such as SIADH, use of diuretics or drugs associated with inappropriate antidiuretic hormone secretion, adrenal insufficiency, hypothyroidism, primary polydipsia, and edema (e.g., due to liver cirrhosis, congestive heart failure, or nephrotic syndrome). Serum sodium levels should be monitored during maintenance therapy, and patients should be monitored for signs and symptoms possibly indicating hyponatremia such as nausea, malaise, headache, lethargy, confusion, obtundation, and increase in seizure frequency or severity. If hyponatremia occurs, conservative measures such as fluid restriction, a reduction in dosage, or discontinuation of therapy will usually suffice.

Aromatic antiepileptic drugs such as phenytoin, carbamazepine, and oxcarbazepine, inhibit voltage- gated sodium channels and reduce membrane excitability in neurons and muscle and can be associated with cardiovascular effects. Individual agents have demonstrated AV heart block, including second and third-degree block following treatment. This occurred generally, but not solely in patients with underlying EKG abnormalities or risk factors for conduction abnormalities. Therapy with these agents should be considered and administered cautiously in patients with a history of cardiovascular disease and conduction abnormalities.

All antidepressants may occasionally cause mania or hypomania, particularly in patients with bipolar disorder. Therapy with antidepressants should be administered cautiously in patients with a history of mania/hypomania.

Rare events of pancytopenia, leukopenia, and agranulocytosis have been reported in patients treated with oxcarbazepine during postmarketing observations. Discontinuation of the drug should be considered if any evidence of these hematologic events develop. Therapy with oxcarbazepine should be administered with caution in patients with preexisting blood dyscrasias and/or bone marrow depression. Complete blood counts, including platelets and possibly reticulocytes and serum iron, should be performed prior to initiating therapy and regularly during therapy.

Aromatic antiepileptic drugs such as phenytoin, carbamazepine, and oxcarbazepine, inhibit voltage- gated sodium channels and reduce membrane excitability in neurons and muscle and can be associated with cardiovascular effects. Individual agents have demonstrated AV heart block, including second and third-degree block following treatment. This occurred generally, but not solely in patients with underlying EKG abnormalities or risk factors for conduction abnormalities. Therapy with these agents should be considered and administered cautiously in patients with a history of cardiovascular disease and conduction abnormalities.

Some anticonvulsants can cause clinically significant hyponatremia (Na < 125 mmol/L). Therapy with these drugs should be administered cautiously in patients with conditions predisposing to hyponatremia, such as SIADH, use of diuretics or drugs associated with inappropriate antidiuretic hormone secretion, adrenal insufficiency, hypothyroidism, primary polydipsia, and edema (e.g., due to liver cirrhosis, congestive heart failure, or nephrotic syndrome). Serum sodium levels should be monitored during maintenance therapy, and patients should be monitored for signs and symptoms possibly indicating hyponatremia such as nausea, malaise, headache, lethargy, confusion, obtundation, and increase in seizure frequency or severity. If hyponatremia occurs, conservative measures such as fluid restriction, a reduction in dosage, or discontinuation of therapy will usually suffice.

Some anticonvulsants can cause clinically significant hyponatremia (Na < 125 mmol/L). Therapy with these drugs should be administered cautiously in patients with conditions predisposing to hyponatremia, such as SIADH, use of diuretics or drugs associated with inappropriate antidiuretic hormone secretion, adrenal insufficiency, hypothyroidism, primary polydipsia, and edema (e.g., due to liver cirrhosis, congestive heart failure, or nephrotic syndrome). Serum sodium levels should be monitored during maintenance therapy, and patients should be monitored for signs and symptoms possibly indicating hyponatremia such as nausea, malaise, headache, lethargy, confusion, obtundation, and increase in seizure frequency or severity. If hyponatremia occurs, conservative measures such as fluid restriction, a reduction in dosage, or discontinuation of therapy will usually suffice.

Treatment with mirtazapine can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

Some anticonvulsants can cause clinically significant hyponatremia (Na < 125 mmol/L). Therapy with these drugs should be administered cautiously in patients with conditions predisposing to hyponatremia, such as SIADH, use of diuretics or drugs associated with inappropriate antidiuretic hormone secretion, adrenal insufficiency, hypothyroidism, primary polydipsia, and edema (e.g., due to liver cirrhosis, congestive heart failure, or nephrotic syndrome). Serum sodium levels should be monitored during maintenance therapy, and patients should be monitored for signs and symptoms possibly indicating hyponatremia such as nausea, malaise, headache, lethargy, confusion, obtundation, and increase in seizure frequency or severity. If hyponatremia occurs, conservative measures such as fluid restriction, a reduction in dosage, or discontinuation of therapy will usually suffice.

Tetracyclic antidepressants as other type of antidepressants have an effect on pupil size causing dilation. This effect can potentially narrow the eye angle resulting in increased intraocular pressure and angle closure glaucoma, especially in predisposed patients. These drugs should be used with caution in patients with anatomically narrow angle or history of glaucoma.

Mirtazapine may significantly elevate serum triglyceride and total cholesterol levels. Patients with preexisting hyperlipidemia may require closer monitoring during mirtazapine therapy, and adjustments made accordingly in their lipid-lowering regimen.

Some anticonvulsants can cause clinically significant hyponatremia (Na < 125 mmol/L). Therapy with these drugs should be administered cautiously in patients with conditions predisposing to hyponatremia, such as SIADH, use of diuretics or drugs associated with inappropriate antidiuretic hormone secretion, adrenal insufficiency, hypothyroidism, primary polydipsia, and edema (e.g., due to liver cirrhosis, congestive heart failure, or nephrotic syndrome). Serum sodium levels should be monitored during maintenance therapy, and patients should be monitored for signs and symptoms possibly indicating hyponatremia such as nausea, malaise, headache, lethargy, confusion, obtundation, and increase in seizure frequency or severity. If hyponatremia occurs, conservative measures such as fluid restriction, a reduction in dosage, or discontinuation of therapy will usually suffice.

Treatment with mirtazapine can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted.

Some anticonvulsants can cause clinically significant hyponatremia (Na < 125 mmol/L). Therapy with these drugs should be administered cautiously in patients with conditions predisposing to hyponatremia, such as SIADH, use of diuretics or drugs associated with inappropriate antidiuretic hormone secretion, adrenal insufficiency, hypothyroidism, primary polydipsia, and edema (e.g., due to liver cirrhosis, congestive heart failure, or nephrotic syndrome). Serum sodium levels should be monitored during maintenance therapy, and patients should be monitored for signs and symptoms possibly indicating hyponatremia such as nausea, malaise, headache, lethargy, confusion, obtundation, and increase in seizure frequency or severity. If hyponatremia occurs, conservative measures such as fluid restriction, a reduction in dosage, or discontinuation of therapy will usually suffice.

The use of mirtazapine has occasionally been associated with ALT (SGPT) elevations greater than three times the upper limit of normal. Although the majority of cases were reversible (some despite continued treatment) and not associated with other signs or symptoms suggestive of hepatic injury, therapy with mirtazapine should be administered cautiously in patients with preexisting liver disease. Periodic monitoring of liver enzyme levels is recommended.

Activation of mania/hypomania has been reported during treatment with mirtazapine. Although the incidence has been low (0.2%), mirtazapine should be used carefully in patients with history of mania/hypomania.

All antidepressants may occasionally cause mania or hypomania, particularly in patients with bipolar disorder. Therapy with antidepressants should be administered cautiously in patients with a history of mania/hypomania.

Some anticonvulsants can cause clinically significant hyponatremia (Na < 125 mmol/L). Therapy with these drugs should be administered cautiously in patients with conditions predisposing to hyponatremia, such as SIADH, use of diuretics or drugs associated with inappropriate antidiuretic hormone secretion, adrenal insufficiency, hypothyroidism, primary polydipsia, and edema (e.g., due to liver cirrhosis, congestive heart failure, or nephrotic syndrome). Serum sodium levels should be monitored during maintenance therapy, and patients should be monitored for signs and symptoms possibly indicating hyponatremia such as nausea, malaise, headache, lethargy, confusion, obtundation, and increase in seizure frequency or severity. If hyponatremia occurs, conservative measures such as fluid restriction, a reduction in dosage, or discontinuation of therapy will usually suffice.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

Some anticonvulsants can cause clinically significant hyponatremia (Na < 125 mmol/L). Therapy with these drugs should be administered cautiously in patients with conditions predisposing to hyponatremia, such as SIADH, use of diuretics or drugs associated with inappropriate antidiuretic hormone secretion, adrenal insufficiency, hypothyroidism, primary polydipsia, and edema (e.g., due to liver cirrhosis, congestive heart failure, or nephrotic syndrome). Serum sodium levels should be monitored during maintenance therapy, and patients should be monitored for signs and symptoms possibly indicating hyponatremia such as nausea, malaise, headache, lethargy, confusion, obtundation, and increase in seizure frequency or severity. If hyponatremia occurs, conservative measures such as fluid restriction, a reduction in dosage, or discontinuation of therapy will usually suffice.

The use of tricyclic and tetracyclic antidepressants is associated with a risk of seizures. Only one case of seizure was reported with mirtazapine, a newer tetracyclic antidepressant, during premarketing trials involving nearly 2800 patients. However, the drug has not been evaluated in controlled studies of patients with a history of seizures. Therapy with mirtazapine should be administered cautiously in such patients.

Some anticonvulsants can cause clinically significant hyponatremia (Na < 125 mmol/L). Therapy with these drugs should be administered cautiously in patients with conditions predisposing to hyponatremia, such as SIADH, use of diuretics or drugs associated with inappropriate antidiuretic hormone secretion, adrenal insufficiency, hypothyroidism, primary polydipsia, and edema (e.g., due to liver cirrhosis, congestive heart failure, or nephrotic syndrome). Serum sodium levels should be monitored during maintenance therapy, and patients should be monitored for signs and symptoms possibly indicating hyponatremia such as nausea, malaise, headache, lethargy, confusion, obtundation, and increase in seizure frequency or severity. If hyponatremia occurs, conservative measures such as fluid restriction, a reduction in dosage, or discontinuation of therapy will usually suffice.

Decreased values for thyroid function tests, especially T4 have been observed with the administration of oxcarbazepine. This should be taken into account in patients with thyroid disorders.