Drug Interactions between fluconazole and lithium

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

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

MONITOR: One study has suggested that caffeine withdrawal may significantly increase blood lithium levels. The mechanism may be involve reversal of a caffeine-induced increase in renal lithium excretion.

MANAGEMENT: When caffeine is eliminated from the diet of lithium-treated patients, caution should be exercised. When caffeine consumption is decreased, close observation for evidence of lithium toxicity and worsening of the psychiatric disorder is recommended. Patients should be advised to notify their physician if they experience symptoms of possible lithium toxicity such as drowsiness, dizziness, weakness, ataxia, tremor, vomiting, diarrhea, thirst, blurry vision, tinnitus, or increased urination.

Antipsychotics can lower the seizure threshold and trigger seizures in a dose-dependent manner. Seizures have been reported in patients receiving antipsychotic therapy and may occur in epileptic patients even with maintenance of routine anticonvulsant treatment. Therapy with antipsychotics should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism. High dosages should be avoided if possible.

Lithium should generally not be given to patients with significant cardiovascular disease since the risk of lithium toxicity is high in these patients. Additionally, there have been postmarketing reports of a possible association between lithium therapy and the unmasking of Brugada Syndrome, a disorder characterized by abnormal EKG findings and a risk of sudden death. Lithium should be avoided in patients with this diagnosis or suspicion of it, or that have risk factors, which include unexplained syncope, family history of this syndrome, or family history of unexplained sudden death before the age of 45 years.
Therapy with lithium should be administered with extreme caution in patients with preexisting cardiac disease. Consultation with a cardiologist is highly recommended and cardiac monitoring should be completed before and during treatment.

Antipsychotics can lower the seizure threshold and trigger seizures in a dose-dependent manner. Seizures have been reported in patients receiving antipsychotic therapy and may occur in epileptic patients even with maintenance of routine anticonvulsant treatment. Therapy with antipsychotics should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism. High dosages should be avoided if possible.

Lithium reduces the ability of the kidney to concentrate urine and produces a mild diabetes insipidus and polyuria. Therefore, patients with preexisting dehydration are more prone to lithium retention and toxicity. Therapy with lithium should be administered cautiously in dehydrated patients and may need to be discontinued until improvement in hydration status. Careful monitoring of lithium levels are recommended. Patients with sweating, diarrhea or concomitant infection with fever may need a temporary reduction or cessation of medication.

Antipsychotic drugs are not approved for the treatment of patients with dementia-related psychosis. Older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death; although the causes were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. A causal relationship with antipsychotic use has not been established. In controlled trials in older patients with dementia-related psychosis, patients randomized to risperidone, aripiprazole, and olanzapine had higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, compared to patients treated with placebo.

Lithium reduces the ability of the kidney to concentrate urine and produces a mild diabetes insipidus and polyuria. Therefore, patients with preexisting dehydration are more prone to lithium retention and toxicity. Therapy with lithium should be administered cautiously in dehydrated patients and may need to be discontinued until improvement in hydration status. Careful monitoring of lithium levels are recommended. Patients with sweating, diarrhea or concomitant infection with fever may need a temporary reduction or cessation of medication.

The risk for lithium toxicity may be increased in patients with diarrhea and excessive sweating. Dehydration and sodium depletion may occur in these patients leading to lithium retention and toxicity. The use of lithium may need to be reduced or suspended until the condition resolves. Supplemental fluid and salt may need to be administered. Monitoring serum lithium levels is recommended.

Lithium reduces the ability of the kidney to concentrate urine and produces a mild diabetes insipidus and polyuria. Therefore, patients with preexisting dehydration are more prone to lithium retention and toxicity. Therapy with lithium should be administered cautiously in dehydrated patients and may need to be discontinued until improvement in hydration status. Careful monitoring of lithium levels are recommended. Patients with sweating, diarrhea or concomitant infection with fever may need a temporary reduction or cessation of medication.

Lithium reduces the ability of the kidney to concentrate urine and produces a mild diabetes insipidus and polyuria. Therefore, patients with preexisting dehydration are more prone to lithium retention and toxicity. Therapy with lithium should be administered cautiously in dehydrated patients and may need to be discontinued until improvement in hydration status. Careful monitoring of lithium levels are recommended. Patients with sweating, diarrhea or concomitant infection with fever may need a temporary reduction or cessation of medication.

The risk for lithium toxicity may be increased in patients with diarrhea and excessive sweating. Dehydration and sodium depletion may occur in these patients leading to lithium retention and toxicity. The use of lithium may need to be reduced or suspended until the condition resolves. Supplemental fluid and salt may need to be administered. Monitoring serum lithium levels is recommended.

Lithium decreases sodium reabsorption by the renal tubules which could lead to sodium depletion. Therapy with lithium should be administered cautiously in patients with preexisting sodium depletion as the risk of lithium toxicity is increased. Lower dosages may be required. Patients should maintain a normal diet, including salt, and an adequate fluid intake. Monitoring lithium serum concentrations is recommended.

The use of lithium has been associated with hypothyroidism in 5% to 15% of patient as it blocks the release of thyroxine (T4) and triiodothyronine (T3) mediated by thyrotropin. Therapy with lithium should be administered cautiously in patients with preexisting hypothyroidism. Careful monitoring of the thyroid function is recommended and supplemental thyroid treatment may be required.

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.

Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with the use of antipsychotic drugs. The diagnostic evaluation is complicated and the management requires immediate discontinuation of the antipsychotic therapy and intensive symptomatic treatment and medical monitoring. If a patient that has recovered from NMS requires antipsychotic drug treatment again, the reintroduction of therapy should be carefully considered as NMS recurrences have been reported.

Lithium is primarily eliminated by the kidneys and should generally not be administered to patients with significant renal dysfunction. Additionally, morphological changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy, although the association has not been clearly established. Kidney function should be assessed in patients prior to starting therapy, during and thereafter and routine urinalysis and renal function tests are recommended. Progressive or sudden changes in renal function indicate the need for reevaluation of treatment. Monitoring lithium serum levels is also recommended.

Lithium should generally not be given to patients with significant cardiovascular disease since the risk of lithium toxicity is high in these patients. Additionally, there have been postmarketing reports of a possible association between lithium therapy and the unmasking of Brugada Syndrome, a disorder characterized by abnormal EKG findings and a risk of sudden death. Lithium should be avoided in patients with this diagnosis or suspicion of it, or that have risk factors, which include unexplained syncope, family history of this syndrome, or family history of unexplained sudden death before the age of 45 years.
Therapy with lithium should be administered with extreme caution in patients with preexisting cardiac disease. Consultation with a cardiologist is highly recommended and cardiac monitoring should be completed before and during treatment.

Lithium should generally not be given to patients with significant cardiovascular disease since the risk of lithium toxicity is high in these patients. Additionally, there have been postmarketing reports of a possible association between lithium therapy and the unmasking of Brugada Syndrome, a disorder characterized by abnormal EKG findings and a risk of sudden death. Lithium should be avoided in patients with this diagnosis or suspicion of it, or that have risk factors, which include unexplained syncope, family history of this syndrome, or family history of unexplained sudden death before the age of 45 years.
Therapy with lithium should be administered with extreme caution in patients with preexisting cardiac disease. Consultation with a cardiologist is highly recommended and cardiac monitoring should be completed before and during treatment.

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.

Antipsychotic drugs can elevate serum prolactin concentrations, and this elevation persists during chronic administration. This should be considered if therapy will be prescribed in patients with previously detected breast cancer as one-third of human breast cancers are prolactin-dependent in vitro. Associated disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported. Appropriate laboratory testing and follow-up is advised.

Patients with fever may have a lower tolerance to lithium due to increased fluid and sodium loss. Lithium dosage may need to be reduced or suspended in such patients. Monitoring lithium serum levels is recommended.

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.

Antipsychotic drugs can elevate serum prolactin concentrations, and this elevation persists during chronic administration. This should be considered if therapy will be prescribed in patients with previously detected breast cancer as one-third of human breast cancers are prolactin-dependent in vitro. Associated disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported. Appropriate laboratory testing and follow-up is advised.

The use of antipsychotics has been associated with events of leukopenia, neutropenia and agranulocytosis. Possible risk factors include preexisting low white blood cell count, and history of drug induced leukopenia/neutropenia. Patients with these risk factors should have complete blood count monitored frequently during the first few months of therapy. Patients should also be monitored for any signs or symptoms of infection. 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 or severe neutropenia (ANC < 1000/mm3).

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.