Drug Interactions between fluconazole and phenobarbital

Ask your doctor before using PHENobarbital together with ethanol (alcohol), this can add to dizziness, drowsiness and other side effects of PHENobarbital. Be careful if you drive or do activities that require you to be awake and alert. Talk with your doctor before using any medications together, or drinking alcohol with PHENobarbital. 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.

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.

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.

Barbiturates should not be administered by injection to patients in shock or coma or who have recently received another respiratory depressant. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.

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.

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.

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 intravenous administration of barbiturates may produce severe cardiovascular reactions such as bradycardia, hypertension, or vasodilation with fall in blood pressure, particularly during rapid infusion. Parenteral therapy with barbiturates should be administered cautiously in patients with hypertension, hypotension, or cardiac disease. The intravenous administration of barbiturates should be reserved for emergency treatment of acute seizures or for anesthesia.

The intravenous administration of barbiturates may produce severe cardiovascular reactions such as bradycardia, hypertension, or vasodilation with fall in blood pressure, particularly during rapid infusion. Parenteral therapy with barbiturates should be administered cautiously in patients with hypertension, hypotension, or cardiac disease. The intravenous administration of barbiturates should be reserved for emergency treatment of acute seizures or for anesthesia.

The intravenous administration of barbiturates may produce severe cardiovascular reactions such as bradycardia, hypertension, or vasodilation with fall in blood pressure, particularly during rapid infusion. Parenteral therapy with barbiturates should be administered cautiously in patients with hypertension, hypotension, or cardiac disease. The intravenous administration of barbiturates should be reserved for emergency treatment of acute seizures or for anesthesia.

The use of fluconazole has been rarely associated with hepatotoxicity. Reversible idiosyncratic hepatitis, cholestasis and fatal fulminant hepatic failure have been reported, the latter occurring primarily in patients with serious underlying medical conditions and taking multiple concomitant medications. Liver function tests should be performed periodically in patients with preexisting hepatic abnormalities, particularly during prolonged therapy. Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

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 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.

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 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.

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.

Barbiturates should not be administered by injection to patients in shock or coma or who have recently received another respiratory depressant. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.

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.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

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.

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.

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.

Fluconazole is substantially removed by hemodialysis. Plasma levels of fluconazole has been shown to reduce by 50% following 3 hours of dialysis. Fluconazole should be administered after hemodialysis.

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.

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.

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.

Fluconazole is primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from fluconazole due to decreased drug clearance. Dosage adjustments are recommended for patients with moderate to severe renal impairment (CrCl <= 50 mL/min) receiving multiple doses of the drug.

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.