Interactions between Bupropion / naltrexone and Mephobarbital

Mephobarbital has a major potential interaction with Acute Alcohol Intoxication.

The use of barbiturates is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of barbiturates may be additive with those of alcohol. Severe respiratory depression and death may occur. Therapy with barbiturates should be administered cautiously in patients who might be prone to acute alcohol intake.

Mephobarbital has a moderate potential interaction with Adrenal Insufficiency.

Barbiturates, especially phenobarbital, secobarbital and butabarbital, may diminish the systemic effects of exogenous and endogenous corticosteroids via induction of hepatic microsomal enzymes, thereby accelerating the metabolism of corticosteroids. In addition, barbiturates may interfere with pituitary corticotropin production. Therapy with barbiturates should be administered cautiously in patients with adrenal insufficiency. Patients with borderline hypoadrenalism should be monitored closely, and patients receiving steroid supplementation may require an adjustment in dosage when barbiturates are added to or withdrawn from their medication regimen.

The buPROPion in bupropion / naltrexone has a major potential interaction with Alcoholism.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

Mephobarbital has a major potential interaction with Alcoholism.

Barbiturates have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use of excessive dosages. Abrupt cessation and/or a reduction in dosage may precipitate withdrawal symptoms. In patients who have developed tolerance to a barbiturate, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with barbiturates. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of barbiturates should be undertaken gradually using a dosage-tapering schedule.

The buPROPion in bupropion / naltrexone has a major potential interaction with Anorexia Nervosa.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

Mephobarbital has a major potential interaction with Asphyxia.

Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with barbiturates should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.

The buPROPion in bupropion / naltrexone has a major potential interaction with Bipolar Disorder.

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials; these trials did not show increased risk in patients older than 24 years and risk was reduced in patients 65 years and older. Adult and pediatric patients with major depressive disorder may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressants; this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders; such disorders are the strongest predictors of suicide. Patients of all ages treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of drug therapy, and at times of dose changes. Family members/caregivers should be advised to monitor for changes in behavior and to notify the health care provider. Changing the therapeutic regimen (including discontinuing the medication) should be considered in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

The buPROPion in bupropion / naltrexone has a moderate potential interaction with Bipolar Disorder.

Bupropion is not approved for the treatment of bipolar depression. Antidepressant therapy can trigger a manic, mixed, or hypomanic episode; the risk appears increased in patients with bipolar disorder or with risk factors for bipolar disorder. Before starting bupropion, patients should be screened for history of bipolar disorder and risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression). Depressed patients treated with bupropion have had various neuropsychiatric signs/symptoms, including delusions, hallucinations, psychosis, concentration disturbance, confusion, and paranoia; some of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated with dose reduction and/or discontinuation of therapy. Bupropion should be discontinued if such reactions occur.

Mephobarbital has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.

Hematologic toxicity, including agranulocytosis, thrombocytopenic purpura and megaloblastic anemia, has been reported rarely during use of barbiturates. Therapy with barbiturates should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Blood counts are recommended prior to and periodically during long-term therapy, and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, easy bruising, petechiae, bleeding, pallor, dizziness, or jaundice. Barbiturate therapy should be discontinued if blood dyscrasias occur.

The buPROPion in bupropion / naltrexone has a major potential interaction with Brain Tumor.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

The buPROPion in bupropion / naltrexone has a major potential interaction with Bulimia.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

The buPROPion in bupropion / naltrexone has a major potential interaction with CNS Infection.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

The buPROPion in bupropion / naltrexone has a major potential interaction with Depression.

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials; these trials did not show increased risk in patients older than 24 years and risk was reduced in patients 65 years and older. Adult and pediatric patients with major depressive disorder may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressants; this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders; such disorders are the strongest predictors of suicide. Patients of all ages treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of drug therapy, and at times of dose changes. Family members/caregivers should be advised to monitor for changes in behavior and to notify the health care provider. Changing the therapeutic regimen (including discontinuing the medication) should be considered in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

Mephobarbital has a moderate potential interaction with Depression.

Barbiturates depress the central nervous system and may cause or exacerbate mental depression. Therapy with barbiturates should be administered cautiously in patients with a history of depression or suicidal tendencies. It may be prudent to refrain from dispensing large quantities of medication to these patients.

Mephobarbital has a moderate potential interaction with Depression.

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.

Mephobarbital has a major potential interaction with Dermatitis, Drug-Induced.

Skin eruptions may precede rare but potentially fatal barbiturate-induced reactions such as systemic lupus erythematosus and exfoliative dermatitis, the latter of which may be accompanied by hepatitis and jaundice. Therapy with barbiturates should be administered cautiously in patients with preexisting drug-induced dermatitis, since it may delay the recognition of a potential reaction to barbiturates. Barbiturate therapy should be withdrawn promptly at the first sign of a dermatologic adverse effect. However, cutaneous reactions may proceed to an irreversible stage even after cessation of medication due to the slow rate of metabolism and excretion of barbiturates. Patients should be advised to promptly report signs that may indicate impending development of barbiturate-related cutaneous lesions, including high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Rashes may be more likely to occur with phenobarbital and mephobarbital.

The buPROPion in bupropion / naltrexone has a major potential interaction with Diabetes Mellitus.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

The buPROPion in bupropion / naltrexone has a major potential interaction with Drug Dependence.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

Mephobarbital has a major potential interaction with Drug Dependence.

Barbiturates have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use of excessive dosages. Abrupt cessation and/or a reduction in dosage may precipitate withdrawal symptoms. In patients who have developed tolerance to a barbiturate, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with barbiturates. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of barbiturates should be undertaken gradually using a dosage-tapering schedule.

The buPROPion in bupropion / naltrexone has a moderate potential interaction with Glaucoma, Narrow Angle.

The pupillary dilation that occurs after use of many antidepressant drugs (including bupropion) can induce increased intraocular pressure and result in angle-closure (narrow-angle) glaucoma in a patient with anatomically narrow angles who does not have a patent iridectomy. Patients may want to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible. The use of antidepressants (including bupropion-dextromethorphan) should be avoided in patients with untreated anatomically narrow angles.

The buPROPion in bupropion / naltrexone has a major potential interaction with Head Injury.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

Mephobarbital has a moderate potential interaction with Hyperkinetic Syndrome of Childhood.

Paradoxical reactions characterized by excitability and restlessness may occur in pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with barbiturates.

The buPROPion in bupropion / naltrexone has a major potential interaction with Hypoglycemia.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

The buPROPion in bupropion / naltrexone has a major potential interaction with Hyponatremia.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

The buPROPion in bupropion / naltrexone has a major potential interaction with Liver Disease.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

The naltrexone in bupropion / naltrexone has a major potential interaction with Liver Disease.

The use of naltrexone is contraindicated in patients with active hepatitis or hepatic failure. Naltrexone has caused direct hepatocellular injury when administered at doses less than or equal to 5 times the recommended once daily 50 mg dose. Therapy with naltrexone should be administered cautiously in patients with active hepatic disease. Clinical monitoring of transaminase levels prior to and during naltrexone therapy is recommended.

Mephobarbital has a major potential interaction with Liver Disease.

Barbiturates are extensively metabolized by the liver. The plasma clearance of barbiturates may be decreased and the half-lives prolonged in patients with impaired hepatic function. Therapy with barbiturates should be administered cautiously and initiated at reduced dosages in patients with liver disease. Barbiturates are not recommended for use in patients with cirrhosis, hepatic failure, hepatic coma, or other severe hepatic impairment.

The buPROPion in bupropion / naltrexone has a moderate potential interaction with Liver Disease.

Bupropion is primarily metabolized by the liver. The systemic exposure and half-life of bupropion and its metabolites may be increased in patients with liver dysfunction. A reduced dose and/or dosing frequency should be considered in patients with mild liver dysfunction (Child-Pugh score: 5 to 6). A dosage reduction is required in patients with moderate to severe liver dysfunction (Child-Pugh score: 7 to 15) who are using a single-ingredient bupropion product; the dosage should not exceed 75 mg/day with immediate-release bupropion hydrochloride (HCl), 100 mg/day or 150 mg every other day with sustained-release bupropion HCl, 150 mg every other day with extended-release bupropion HCl, and 174 mg every other day with extended-release bupropion hydrobromide. Bupropion-dextromethorphan is not recommended for patients with severe liver dysfunction (Child-Pugh C), and no dose adjustment of bupropion-dextromethorphan is recommended in patients with mild or moderate liver dysfunction (Child-Pugh A or B).

The naltrexone in bupropion / naltrexone has a moderate potential interaction with Liver Disease.

Opiate antagonists are metabolized by the liver (naltrexone to an active metabolite) and eliminated by the kidney. Hepatic and renal impairment may reduce the metabolism and clearance of opiate antagonists. Dosage adjustment for single dose administration is not necessary, however, repeated doses in patients with hepatic and/or renal dysfunction may require adjustment.

The buPROPion in bupropion / naltrexone has a minor potential interaction with Malnourishment.

The use of bupropion is associated with weight alterations. Both weight gain and weight loss may occur, although the latter is much more common. Weight loss greater than 2.27 kg was reported in up to 28% of patients, which may be undesirable in patients suffering from anorexia, malnutrition, or excessive weight loss. Weight change should be monitored during therapy if bupropion is used in these patients.

The buPROPion in bupropion / naltrexone has a moderate potential interaction with Mania.

Bupropion is not approved for the treatment of bipolar depression. Antidepressant therapy can trigger a manic, mixed, or hypomanic episode; the risk appears increased in patients with bipolar disorder or with risk factors for bipolar disorder. Before starting bupropion, patients should be screened for history of bipolar disorder and risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression). Depressed patients treated with bupropion have had various neuropsychiatric signs/symptoms, including delusions, hallucinations, psychosis, concentration disturbance, confusion, and paranoia; some of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated with dose reduction and/or discontinuation of therapy. Bupropion should be discontinued if such reactions occur.

Mephobarbital has a moderate potential interaction with Panhypopituitarism.

Barbiturates, especially phenobarbital, secobarbital and butabarbital, may diminish the systemic effects of exogenous and endogenous corticosteroids via induction of hepatic microsomal enzymes, thereby accelerating the metabolism of corticosteroids. In addition, barbiturates may interfere with pituitary corticotropin production. Therapy with barbiturates should be administered cautiously in patients with adrenal insufficiency. Patients with borderline hypoadrenalism should be monitored closely, and patients receiving steroid supplementation may require an adjustment in dosage when barbiturates are added to or withdrawn from their medication regimen.

Mephobarbital has a major potential interaction with Porphyria.

The use of barbiturates is contraindicated in patients with a history of porphyria. Barbiturates may exacerbate acute intermittent porphyria or porphyria variegata by inducing the enzymes responsible for porphyrin synthesis.

Mephobarbital has a moderate potential interaction with Psychosis.

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.

Mephobarbital has a major potential interaction with Pulmonary Impairment.

Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with barbiturates should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.

Mephobarbital has a major potential interaction with Renal Dysfunction.

The long-acting barbiturate, phenobarbital, is partially eliminated by the kidney. The plasma clearance of phenobarbital may be decreased and the half-life prolonged in patients with impaired renal function. Therapy with phenobarbital should be administered cautiously and initiated at reduced dosages in patients with renal impairment. Since approximately 75% of a mephobarbital dose is metabolized to phenobarbital, the same precaution should be observed with mephobarbital. The remaining barbiturates, which are short- and intermediate-acting, are all negligibly excreted in the urine and may be appropriate alternatives in these patients.

The buPROPion in bupropion / naltrexone has a moderate potential interaction with Renal Dysfunction.

Bupropion and its metabolites, some of which are pharmacologically active with one-fifth to one-half the potency of the parent drug, are cleared renally and may accumulate in patients with renal dysfunction (GFR less than 90 mL/min) to a greater extent than usual. Therefore, bupropion should be used with caution in patients with renal dysfunction. A reduced dose and/or dosing frequency should be considered, and patients should be closely monitored for adverse effects that could indicate high bupropion or metabolite exposures. Bupropion-dextromethorphan is not recommended for patients with severe renal dysfunction (estimated GFR 15 to 29 mL/min/1.73 m2); dosage adjustment of bupropion-dextromethorphan is recommended in patients with moderate renal dysfunction (estimated GFR 30 to 59 mL/min/1.73 m2).

The naltrexone in bupropion / naltrexone has a moderate potential interaction with Renal Dysfunction.

Opiate antagonists are metabolized by the liver (naltrexone to an active metabolite) and eliminated by the kidney. Hepatic and renal impairment may reduce the metabolism and clearance of opiate antagonists. Dosage adjustment for single dose administration is not necessary, however, repeated doses in patients with hepatic and/or renal dysfunction may require adjustment.

Mephobarbital has a major potential interaction with Respiratory Arrest.

Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with barbiturates should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.

The buPROPion in bupropion / naltrexone has a major potential interaction with Seizures.

Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. In 1 study, the seizure incidence was about 0.4% with immediate-release bupropion hydrochloride (HCl) in the range of 300 to 450 mg/day (equal to 348 to 522 mg/day of extended-release bupropion hydrobromide [HBr]); the incidence of seizures increases dramatically at higher dosages (almost 10-fold between 450 and 600 mg/day as bupropion HCl [equal to 522 and 696 mg/day as bupropion HBr]). The risk of seizures (related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold) should be considered before starting bupropion. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa (a higher incidence of seizures was observed in such patients treated with immediate-release bupropion) and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions including severe head injury; arteriovenous malformation; CNS infection or CNS tumor; severe stroke; metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia); excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates; use of illicit drugs (e.g., cocaine); abuse/misuse of prescription drugs (e.g., CNS stimulants); diabetes mellitus treated with oral hypoglycemic agents or insulin; use of anorectic agents; and concomitant use of medications that lower the seizure threshold. The risk of seizure can be reduced if the maximum recommended dosage is not exceeded (e.g., 450 mg/day [as 150 mg 3 times a day] for immediate-release bupropion HCl; 400 mg/day [as 200 mg twice a day] for sustained-release bupropion HCl; 450 mg once a day for extended-release bupropion HCl; 522 mg once a day for extended-release bupropion HBr), and the titration rate is gradual. Bupropion should be discontinued and should not be restarted if the patient has a seizure.

Mephobarbital has a moderate potential interaction with Vitamin D Deficiency.

Rickets and osteomalacia have rarely been reported following prolonged use of barbiturates, possibly due to increased metabolism of vitamin D as a result of enzyme induction by barbiturates. Long-term therapy with barbiturates should be administered cautiously in patients with vitamin D deficiency.