Functioning of liver or kidney
Patients with abnormal functioning of the liver are at an increased risk when using Fluzyn. The clearance of Fluzyn is decreased in such patients. A lower dose or taking Fluzyn at alternate days is recommended in such patients.
Discontinuation of treatment with Fluzyn
Patients who discontinue using Fluzyn suddenly are at an increased risk. These patients may develop symptoms including mental discomfort (dysphoric mood), irritability,
nausea, nervousness (agitation),
tremor,
headache,
dizziness, sensory disturbances (electric
shock sensations),
anxiety,
confusion, vomiting, lack of energy (lethargy), emotional changes (lability),
insomnia, and hyperactivity (hypomania) within few days after discontinuation of Fluzyn. Such patients should be monitored for the symptoms occurring on the discontinuation of Fluzyn. Fluzyn should not be discontinued immediately. Its dose should be decreased gradually according to the patient's need. On the occurrence of intolerable symptoms following dose reduction or discontinuation, treatment should be continued with the previously prescribed dose.
Abnormal heartbeat (QT interval prolongation)
Patients with existing heart rhythm disorder (congenital long QT
syndrome), abnormal heartbeat (QT prolongation), family history of heart rhythm disorder, decreased level of
potassium or magnesium in the blood, CYP2D6 poor metabolizer status, heart failure, heart attack, abnormal functioning of the liver, taking highly protein bound drugs, overdose, pimozide, thioridazine, antipsychotics (chlorpromazine, ziprasidone, iloperidone, mesoridazine, haloperidol, phenothiazine and droperidol), certain
antihistamines (astemizole, mizolastine),
antibiotics (erythromycin, moxifloxacin, gatifloxacin and sparfloxacin), procainamide, quinidine, sotalol, amiodarone, pentamidine, methadone, levomethadyl acetate, halofantrine, dolasetron mesylate, probucol, mefloquine, or tacrolimus are at an increased risk when using Fluzyn. These patients are at an increased risk of abnormal heartbeat (QT interval prolongation or Torsades de Pointes). The use of Fluzyn with CYP2D6 inhibitors or highly protein-bound drugs increases the level of Fluzyn in the blood. Precaution should be taken in such patients. Fluzyn should not be used in combination with pimozide, thioridazine, antipsychotics, certain antihistamines, antibiotics, drugs used to treat heart rhythm, pentamidine, methadone, levomethadyl acetate, halofantrine, dolasetron mesylate, probucol, mefloquine, or with tacrolimus. Evaluation and monitoring of the electrocardiogram should be considered in patients with risk factors for prolonged or changes in heartbeat (QT prolongation and ventricular
arrhythmia). If the patient develops symptoms and signs along with the increased or decreased heartbeat, discontinuation of Fluzyn and examination of the heart should be considered.
Disturbances in memory and movement activities (cognitive and motor performance)
Patients using Fluzyn are at an increased risk. These patients may suffer from disturbed thinking, judgment, or movement (motor) skills. The patients should be cautious about
operating heavy machinery until they almost sure that Fluzyn does not affect their ability to work.
Decreased appetite and weight
Underweight depressed patients or patients with an eating disorder (
bulimic patients) are at an increased risk when using Fluzyn. The use of Fluzyn may cause weight loss and anorexia (decreased appetite) in such patients. These patients should be monitored for the change in weight during Fluzyn therapy.
Abnormal bleeding
Patients with a history of
bleeding disorders or using Fluzyn with nonsteroidal anti-inflammatory drugs, aspirin, clozapine, phenothiazines, most tricyclic
antidepressants,
anticoagulants, and warfarin are at an increased risk. Using selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors such as fluoxetine increase the risk of bleeding reactions such as stomach or intestinal, skin, and mucous bleeding. Fluzyn may interfere with serotonin reuptake which may lead to an additional risk of stomach and intestinal bleeding when using Fluzyn with nonsteroidal anti-inflammatory drugs, aspirin, anticoagulants, and warfarin. Bleeding reactions related to selective norepinephrine reuptake inhibitors and serotonin reuptake inhibitors use have been ranged from discoloration of the skin (
ecchymoses), solid blood clot swelling (
hematomas), nose bleeding (
epistaxis) and rupturing of the blood vessels (
hemorrhage). Precaution is advised in patients with a history of bleeding disorders or using Fluzyn with nonsteroidal anti-inflammatory drugs, aspirin, clozapine, anticoagulants, phenothiazines, warfarin, and most tricyclic antidepressants. Patients taking warfarin should be monitored carefully for international normalized ratio when Fluzyn therapy is started or discontinued. Also, dose adjustment should be considered during and after discontinuation of Fluzyn therapy.
Eye disorder (angle-closure glaucoma)
Patients with increased intraocular pressure or with narrow angles without eye
surgery (iridectomy) are at an increased risk when using Fluzyn. These patients are at an increased risk of dilation of the pupil of the eye and angle closure attack (angle-closure
glaucoma). Fluzyn should be used cautiously in such patients.
Low level of sodium in the blood
Elderly patients or patients with an inappropriate amount of
hormone responsible for regulating the level of water in the blood (antidiuretic hormone), with volume-depletion, or taking
diuretics are at an increased risk when using Fluzyn. The use of Fluzyn may cause low levels of
sodium in the blood. Signs and symptoms of low levels of sodium are difficulty in concentrating,
headache, weakness, loss of
memory,
confusion, and unsteadiness which may lead to
falls. Symptoms of more severe or acute cases are
hallucinations, loss of consciousness,
seizure, respiratory arrest,
coma, and fatal. Fluzyn should not be used in these patients. Suitable therapy with Fluzyn should be started in such patients.
Diabetes
Patients with
diabetes are at an increased risk when using Fluzyn. The use or discontinuation of Fluzyn may cause an alteration in glycemic control such as low blood sugar or high blood sugar respectively in such patients. Dose adjustment should be considered in starting or during the discontinuation of Fluzyn therapy. Precaution should be taken in such patients when using Fluzyn.
Suicidal thoughts and behaviors
Children and young adults (age 18 to 24 years) with
depression or other psychotics disorders are at an increased risk when using Fluzyn. These patients may experience worsening of the depression, decreased height, weight gain and are at an increased risk of suicide-related behaviors (suicidal thoughts and
suicide attempt) and hostility (oppositional behavior, predominantly aggression, and anger) when using Fluzyn. Symptoms occurring in the patients during Fluzyn therapy are agitation,
anxiety, panic attacks, irritability,
insomnia, aggressiveness, unfriendly (hostility), acting instantly without thinking (impulsivity), hypomania, movement disorder, and mania. Patients should be monitored closely for the suicidal thoughts, height, weight, and for unusual changes in behavior in the starting of therapy or during dose adjustment. Discontinuation of Fluzyn or changes in the therapy should be considered in such patients. Treatment of Fluzyn should be discontinued slowly, rather discontinuing suddenly, which may lead to the occurrence of the symptoms.
Caregivers and family should be informed about the need to monitor the patients daily for the irritability, agitation, unusual changes in behavior, suicidal thoughts, and for symptoms occurring during Fluzyn therapy. Fluzyn should be prescribed at the lowest effective dose to reduce the risk of overdose. Fluzyn should not be used in children less than 7 years.
Serotonin-inducing symptoms (Serotonin syndrome)
Patients using Fluzyn with neuroleptic drugs, serotonergic drugs (tricyclic
antidepressants, triptans,
lithium, tramadol, tryptophan, fentanyl, buspirone, St. John’s Wort, and amphetamines), drugs altering the metabolism of serotonin, those intended to treat psychiatric disorders (linezolid and intravenous methylene blue) are at an increased risk. These patients are at an increased risk of serotonin
syndrome or neuroleptic
malignant syndrome-like events. Symptoms of serotonin syndrome are
nausea,
diarrhea, vomiting,
hallucinations, agitation,
delirium, increased heartbeat, borderline high blood pressure,
coma, sweating (diaphoresis), increased body temperature,
dizziness, rigidity, flushing, overactive reflexes (hyperreflexia),
seizures, jerky
contraction of muscles (
myoclonus) and incoordination. Such patients should be made aware of increased risk for serotonin syndrome in the starting of therapy and during increased dose. Discontinuation of this combination and starting of suitable treatment is recommended on the occurrence of symptoms of serotonin syndrome. Also, when using or discontinuing this combination, dose reductions and monitoring of tricyclic antidepressants levels in the blood should be considered. Precaution along with close and frequent monitoring is recommended in patients using this combination. Monoamine oxidase inhibitors should not be used in patients who are intended to treat mental disorders with Fluzyn and within 5 weeks of stopping therapy with Fluzyn. Also, monoamine oxidase inhibitors should not be used within 14 days of stopping treatment with Fluzyn. The patient should be monitored for signs of serotonin syndrome for 5 weeks and until 24 hours after the last dose of intravenous methylene blue and linezolid. Fluzyn therapy may be continued 24 hours after the last dose of intravenous methylene blue and linezolid.
Allergic reaction and rash
Patients using Fluzyn are at an increased risk. These patients are at an increased risk of rash,
hives, trouble breathing (bronchospasm/laryngospasm), swelling of the lower layer of the skin,
anaphylaxis, breathing difficulty (
dyspnea) and progressive systemic events (such as inflammation of a blood vessel/
vasculitis and autoimmune disorder/lupus-like
syndrome) involving liver, kidney or lung. Diagnostic finding reported in association with rash include increased white blood cells (leukocytosis),
fever,
pain in joints (arthralgias), swelling due to accumulation of fluid, painful condition of the hands or fingers (carpal tunnel syndrome), fluid-buildup in the lungs (respiratory distress), swollen and enlarged lymph nodes, presence of protein in urine, and increase in transaminase in the blood. Patients may improve on discontinuation of Fluzyn. Fluzyn should not be used on the occurrence of rash for which different cause is not identified.
Bipolar disorder (major depressive episode)
Patients with major
depressive episode are at an increased risk when using Fluzyn. Treating such patients with Fluzyn alone may increase the occurrence of a mixed/manic episode. Before starting the Fluzyn treatment, such patients should be examined for the risk of bipolar disorder which includes a detailed psychiatric history such as family history of
suicide, depression, and bipolar disorder. Fluzyn monotherapy should not be used for the treatment of depressive episodes associated with Bipolar I Disorder. Precaution should be taken in patients with a history of bipolar disorder (hypomania/mania).
Seizures
Patients with a history of
seizures or receiving electroconvulsive therapy (ECT) are at an increased risk when using Fluzyn. The use of Fluzyn may increase the risk of prolonged seizures in these patients. Care and precaution should be taken in such patients. Fluzyn therapy should be discontinued on the occurrence of seizures or increased frequency of seizures. This medicine should not be used in patients with unstable seizure. Monitoring of the patients with
epilepsy should be considered.