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 Fluoxetine. 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 Fluoxetine. Symptoms occurring in the patients during Fluoxetine 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 Fluoxetine or changes in the therapy should be considered in such patients. Treatment of Fluoxetine 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 Fluoxetine therapy. Fluoxetine should be prescribed at the lowest effective dose to reduce the risk of overdose. Fluoxetine should not be used in children less than 7 years.
Serotonin-inducing symptoms (Serotonin syndrome)
Patients using Fluoxetine 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
, 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 Fluoxetine and within 5 weeks of stopping therapy with Fluoxetine. Also, monoamine oxidase inhibitors should not be used within 14 days of stopping treatment with Fluoxetine. 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. Fluoxetine therapy may be continued 24 hours after the last dose of intravenous methylene blue and linezolid.
Allergic reaction and rash
Patients using Fluoxetine 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
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 Fluoxetine. Fluoxetine 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 Fluoxetine. Treating such patients with Fluoxetine alone may increase the occurrence of a mixed/manic episode. Before starting the Fluoxetine 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. Fluoxetine 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).
Patients with a history of seizures
or receiving electroconvulsive therapy (ECT) are at an increased risk when using Fluoxetine. The use of Fluoxetine may increase the risk of prolonged seizures in these patients. Care and precaution should be taken in such patients. Fluoxetine 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.
Decreased appetite and weight
depressed patients or patients with an eating disorder (bulimic
patients) are at an increased risk when using Fluoxetine. The use of Fluoxetine may cause weight loss and anorexia (decreased appetite) in such patients. These patients should be monitored for the change in weight during Fluoxetine therapy.
Patients with a history of bleeding
disorders or using Fluoxetine with nonsteroidal anti-inflammatory drugs, aspirin, clozapine, phenothiazines, most tricyclic antidepressants
, 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. Fluoxetine may interfere with serotonin reuptake which may lead to an additional risk of stomach and intestinal bleeding when using Fluoxetine 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 Fluoxetine 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 Fluoxetine therapy is started or discontinued. Also, dose adjustment should be considered during and after discontinuation of Fluoxetine 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 Fluoxetine. These patients are at an increased risk of dilation of the pupil of the eye and angle closure attack (angle-closure glaucoma
). Fluoxetine 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 Fluoxetine. The use of Fluoxetine 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
, 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. Fluoxetine should not be used in these patients. Suitable therapy with Fluoxetine should be started in such patients.
Patients with diabetes
are at an increased risk when using Fluoxetine. The use or discontinuation of Fluoxetine 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 Fluoxetine therapy. Precaution should be taken in such patients when using Fluoxetine.
Disturbances in memory and movement activities (cognitive and motor performance)
Patients using Fluoxetine 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 Fluoxetine does not affect their ability to work.
Functioning of liver or kidney
Patients with abnormal functioning of the liver are at an increased risk when using Fluoxetine. The clearance of Fluoxetine is decreased in such patients. A lower dose or taking Fluoxetine at alternate days is recommended in such patients.
Discontinuation of treatment with Fluoxetine
Patients who discontinue using Fluoxetine suddenly are at an increased risk. These patients may develop symptoms including mental discomfort (dysphoric mood), irritability, nausea
, nervousness (agitation), tremor
, sensory disturbances (electric shock
, vomiting, lack of energy (lethargy), emotional changes (lability), insomnia
, and hyperactivity (hypomania) within few days after discontinuation of Fluoxetine. Such patients should be monitored for the symptoms occurring on the discontinuation of Fluoxetine. Fluoxetine 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 Fluoxetine. These patients are at an increased risk of abnormal heartbeat (QT interval prolongation or Torsades de Pointes). The use of Fluoxetine with CYP2D6 inhibitors or highly protein-bound drugs increases the level of Fluoxetine in the blood. Precaution should be taken in such patients. Fluoxetine 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 Fluoxetine and examination of the heart should be considered.