Sarafem Information
Sarafem (Fluoxetine hydrochloride) Suicidality And Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Sarafem (Fluoxetine hydrochloride) or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Sarafem (Fluoxetine hydrochloride) is not approved for use in pediatric patients. ( : Clinical Worsening and Suicide Risk, : , and : )
Sarafem (Fluoxetine hydrochloride) Description
Sarafem (Fluoxetine hydrochloride) (fluoxetine hydrochloride tablets) is a selective serotonin reuptake inhibitor (SSRI) for oral administration. It is designated (±)-N-methyl-3-phenyl-3-[(α,α,α-trifluoro--tolyl)oxy]propylamine hydrochloride and has the empirical formula of CHFNO•HCl. Its molecular weight is 345.79. The structural formula is:
Fluoxetine hydrochloride is a white to off-white crystalline solid with a solubility of 14 mg/mL in water.
Each Sarafem (Fluoxetine hydrochloride) tablet contains fluoxetine hydrochloride equivalent to 10 mg (32.3 µmol), 15 mg (48.5 µmol) or 20 mg (64.7 µmol) of fluoxetine. Each tablet also contains microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, FD&C Yellow No. 6 aluminum lake (10 mg and 20 mg tablets) and D&C Yellow No. 10 aluminum lake (10 mg and 20 mg tablets).
Sarafem (Fluoxetine hydrochloride) Clinical Pharmacology
The mechanism of action of fluoxetine in premenstrual dysphoric disorder (PMDD) is unknown, but is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Studies at clinically relevant doses in humans have demonstrated that fluoxetine blocks the uptake of serotonin into human platelets. Studies in animals also suggest that fluoxetine is a much more potent uptake inhibitor of serotonin than of norepinephrine.
Antagonism of muscarinic, histaminergic, and α-adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects of certain psychoactive drugs. Fluoxetine has little affinity for these receptors.
Absorption
Food does not appear to affect the systemic bioavailability of fluoxetine, although it may delay its absorption inconsequentially. Thus, fluoxetine may be administered with or without food.
1
PRECAUTIONS
Clinical issues related to metabolism/elimination
Because fluoxetine’s metabolism, like that of a number of other compounds including TCAs and other SSRIs, involves the CYP2D6 system, concomitant therapy with drugs also metabolized by this enzyme system (such as the TCAs) may lead to drug interactions (
).
Excretion
Accumulation and slow elimination
The long elimination half-lives of fluoxetine and norfluoxetine assure that, even when dosing is stopped, active drug substance will persist in the body for weeks (primarily depending on individual patient characteristics, previous dosing regimen, and length of previous therapy at discontinuation). This is of potential consequence when drug discontinuation is required or when drugs are prescribed that might interact with fluoxetine and norfluoxetine following the discontinuation of Sarafem (Fluoxetine hydrochloride) .
Geriatric:
Sarafem (Fluoxetine hydrochloride) Indications And Usage
Sarafem (Fluoxetine hydrochloride) is indicated for the treatment of premenstrual dysphoric disorder (PMDD).
The efficacy of fluoxetine in the treatment of PMDD was established in 3 placebo-controlled trials ( ).
The essential features of PMDD, according to the DSM-IV, include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating, and weight gain. These symptoms occur regularly during the luteal phase and remit within a few days following onset of menses; the disturbance markedly interferes with work or school or with usual social activities and relationships with others. In making the diagnosis, care should be taken to rule out other cyclical mood disorders that may be exacerbated by treatment with an antidepressant.
The effectiveness of Sarafem (Fluoxetine hydrochloride) in long-term use, that is, for more than 6 months, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Sarafem (Fluoxetine hydrochloride) for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Sarafem (Fluoxetine hydrochloride) Contraindications
Sarafem (Fluoxetine hydrochloride) is contraindicated in patients known to be hypersensitive to it.
Sarafem (Fluoxetine hydrochloride) Warnings
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 2.
No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (
and – Discontinuation of Treatment with Sarafem (Fluoxetine hydrochloride) , for a description of the risks of discontinuation of Sarafem (Fluoxetine hydrochloride) ).
In US fluoxetine clinical trials for conditions other than PMDD, 7% of 10,782 patients developed various types of rashes and/or urticaria. Among the cases of rash and/or urticaria reported in premarketing clinical trials, almost a third were withdrawn from treatment because of the rash and/or systemic signs or symptoms associated with the rash. Clinical findings reported in association with rash include fever, leukocytosis, arthralgias, edema, carpal tunnel syndrome, respiratory distress, lymphadenopathy, proteinuria, and mild transaminase elevation. Most patients improved promptly with discontinuation of fluoxetine and/or adjunctive treatment with antihistamines or steroids, and all patients experiencing these events were reported to recover completely.
In premarketing clinical trials of fluoxetine for conditions other than PMDD, 2 patients are known to have developed a serious cutaneous systemic illness. In neither patient was there an unequivocal diagnosis, but one was considered to have a leukocytoclastic vasculitis, and the other, a severe desquamating syndrome that was considered variously to be a vasculitis or erythema multiforme. Other patients have had systemic syndromes suggestive of serum sickness.
Since the introduction of fluoxetine for other indications, systemic events, possibly related to vasculitis and including lupus-like syndrome, have developed in patients with rash. Although these events are rare, they may be serious, involving the lung, kidney, or liver. Death has been reported to occur in association with these systemic events.
Anaphylactoid events, including bronchospasm, angioedema, laryngospasm, and urticaria alone and in combination, have been reported.
Pulmonary events, including inflammatory processes of varying histopathology and/or fibrosis, have been reported rarely. These events have occurred with dyspnea as the only preceding symptom.
Whether these systemic events and rash have a common underlying cause or are due to different etiologies or pathogenic processes is not known. Furthermore, a specific underlying immunologic basis for these events has not been identified. Upon the appearance of rash or of other possibly allergic phenomena for which an alternative etiology cannot be identified, Sarafem (Fluoxetine hydrochloride) should be discontinued.
The concomitant use of Sarafem (Fluoxetine hydrochloride) with MAOIs intended to treat depression is contraindicated (
).
If concomitant treatment of Sarafem (Fluoxetine hydrochloride) with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (
).
The concomitant use of Sarafem (Fluoxetine hydrochloride) with serotonin precursors (such as tryptophan) is not recommended (
).
Thioridazine administration produces a dose-related prolongation of the QT interval, which is associated with serious ventricular arrhythmias, such as torsades de pointes-type arrhythmias, and sudden death. This risk is expected to increase with fluoxetine-induced inhibition of thioridazine metabolism ( ). Thioridazine should not be administered with Sarafem (Fluoxetine hydrochloride) or within a minimum of 5 weeks after Sarafem (Fluoxetine hydrochloride) has been discontinued.
Sarafem (Fluoxetine hydrochloride) Precautions
Abnormal Bleeding
Patient should be cautioned about the risk of bleeding associated with the concomitant use of fluoxetine and NSAIDs, aspirin, or other drugs that affect coagulation (
).
Activation of Mania/Hypomania
Hyponatremia
Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. More severe and/or acute cases have been associated with hallucination, syncope, seizure, coma, respiratory arrest, and death.
Seizures
Use in Patients with Concomitant Illness
Fluoxetine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were systematically excluded from clinical studies during the product’s premarket testing. However, the electrocardiograms of 312 patients who received fluoxetine in double-blind trials for a condition other than PMDD were retrospectively evaluated; no conduction abnormalities that resulted in heart block were observed. The mean heart rate was reduced by approximately 3 beats/min.
In subjects with cirrhosis of the liver, the clearances of fluoxetine and its active metabolite, norfluoxetine, were decreased, thus increasing the elimination half-lives of these substances ( Liver disease
, ). A lower or less frequent dose should be used in patients with cirrhosis ( ).
Studies in depressed patients on dialysis did not reveal excessive accumulation of fluoxetine or norfluoxetine in plasma ( Renal disease
, ). Use of a lower or less frequent dose for renally impaired patients is not routinely necessary ( ).
In patients with diabetes, fluoxetine may alter glycemic control. Hypoglycemia has occurred during therapy with fluoxetine, and hyperglycemia has developed following discontinuation of the drug. As is true with many other types of medication when taken concurrently by patients with diabetes, insulin and/or oral hypoglycemic dosage may need to be adjusted when therapy with fluoxetine is instituted or discontinued.
DOSAGE AND ADMINISTRATION
Interference with Cognitive and Motor Performance
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Sarafem (Fluoxetine hydrochloride) and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for Sarafem (Fluoxetine hydrochloride) . The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Sarafem (Fluoxetine hydrochloride) .
PRECAUTIONS
Clinical Worsening and Suicide Risk
Serotonin Syndrome
As with all drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc.) is a possibility ( Accumulation and slow elimination
).
CLINICAL PHARMACOLOGY
Fluoxetine, inhibits the activity of CYP2D6 and thus may make individuals with normal CYP2D6 metabolic activity resemble a poor metabolizer. Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution. Therapy with medications that are predominantly metabolized by the CYP2D6 system and that have a relatively narrow therapeutic index (see list below) should be initiated at the low end of the dose range if a patient is receiving fluoxetine concurrently or has taken it in the previous 5 weeks. Thus, her dosing requirements resemble those of poor metabolizers. If fluoxetine is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need for decreased dose of the original medication should be considered. Drugs with a narrow therapeutic index represent the greatest concern (e.g., flecainide, propafenone, vinblastine, and TCAs). Due to the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued (
).
Drugs metabolized by CYP3A4
CLINICAL PHARMACOLOGY
Anticonvulsants
CLINICAL PHARMACOLOGY
Lithium
Tryptophan
CONTRAINDICATIONS
WARNINGS
CLINICAL PHARMACOLOGY
Drugs that interfere with hemostasis (e.g., NSAIDs, Aspirin, Warfarin)
Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or SNRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when fluoxetine is initiated or discontinued.
Electroconvulsive therapy (ECT)
There is no evidence of carcinogenicity or mutagenicity from in vitro or animal studies.
Carcinogenicity
2
Mutagenicity
2
Pediatric Use
Pregnancy Category C
CONTRAINDICATIONS
Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20 week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. There is currently no corroborative evidence regarding the risk for PPHN following exposure to SSRIs in pregnancy; this is the first study that has investigated the potential risk. The study did not include enough cases with exposure to individual SSRIs to determine if all SSRIs posed similar levels of PPHN risk.
When treating a pregnant woman with fluoxetine during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment (
). Physicians should note that in a prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication.
Safety and effectiveness in the pediatric population have not been established (
, Clinical Worsening and Suicide Risk). Anyone considering the use of Sarafem (Fluoxetine hydrochloride) in a child or adolescent must balance the potential risks with the clinical need.
Significant toxicity, including myotoxicity, long term neurobehavioral and reproductive toxicity, and impaired bone development, has been observed following exposure of juvenile animals to fluoxetine. Some of these effects occurred at clinically relevant exposures.
In a study in which fluoxetine (3, 10, or 30 mg/kg) was orally administered to young rats from weaning (Postnatal Day 21) through adulthood (Day 90), male and female sexual development was delayed at all doses, and growth (body weight gain, femur length) was decreased during the dosing period in animals receiving the highest dose. At the end of the treatment period, serum levels of creatine kinase (marker of muscle damage) were increased at the intermediate and high doses, and abnormal muscle and reproductive organ histopathology (skeletal muscle degeneration and necrosis, testicular degeneration and necrosis, epididymal vacuolation and hypospermia) was observed at the high dose. When animals were evaluated after a recovery period (up to 11 weeks after cessation of dosing), neurobehavioral abnormalities (decreased reactivity at all doses and learning deficit at the high dose) and reproductive functional impairment (decreased mating at all doses and impaired fertility at the high dose) were seen; in addition, testicular and epididymal microscopic lesions and decreased sperm concentrations were found in the high dose group, indicating that the reproductive organ effects seen at the end of treatment were irreversible. The reversibility of fluoxetine induced muscle damage was not assessed. Adverse effects similar to those observed in rats treated with fluoxetine during the juvenile period have not been reported after administration of fluoxetine to adult animals. Plasma exposures (AUC) to fluoxetine in juvenile rats receiving the low, intermediate, and high dose in this study were approximately 0.1-0.2, 1-2, and 5-10 times, respectively, the average exposure in pediatric patients receiving the maximum recommended dose (MRD) of 20 mg/day. Rat exposures to the major metabolite, norfluoxetine, were approximately 0.3-0.8, 1-8, and 3-20 times, respectively, pediatric exposure at the MRD.
A specific effect of fluoxetine on bone development has been reported in mice treated with fluoxetine during the juvenile period. When mice were treated with fluoxetine (5 or 20 mg/kg, intraperitoneal) for 4 weeks starting at 4 weeks of age, bone formation was reduced resulting in decreased bone mineral content and density. These doses did not affect overall growth (body weight gain or femoral length). The doses administered to juvenile mice in this study are approximately 0.5 and 2 times the MRD for pediatric patients on a body surface area (mg/m) basis.
In another mouse study, administration of fluoxetine (10 mg/kg intraperitoneal) during early postnatal development (Postnatal Days 4 to 21) produced abnormal emotional behaviors (decreased exploratory behavior in elevated plus maze, increased shock avoidance latency) in adulthood (12 weeks of age). The dose used in this study is approximately equal to the pediatric MRD on a mg/m basis. Because of the early dosing period in this study, the significance of these findings to the approved pediatric use in humans is uncertain.
Sarafem (Fluoxetine hydrochloride) Adverse Reactions
In 1 of 3 placebo-controlled, continuous-dosing trials and 1 placebo-controlled, intermittent-dosing trial of fluoxetine in PMDD, treatment-emergent adverse events reporting rates were assessed. The information from Table 3 included under is based on data from the continuous-dosing trial at the recommended dose of Sarafem (Fluoxetine hydrochloride) (Sarafem (Fluoxetine hydrochloride) 20 mg, N = 104; placebo, N = 108) and data from the intermittent-dosing trial of fluoxetine in PMDD (Sarafem (Fluoxetine hydrochloride) 20 mg, N = 86; placebo, N = 88). In addition, a broader set of information on treatment-emergent adverse events in the population of female patients, 18 to 45 years of age from the US placebo-controlled depression, OCD, and bulimia clinical trials, is presented for comparison ( ).
Adverse events were recorded by clinical investigators using descriptive terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a limited (i.e., reduced) number of standardized event categories.
In the tables and tabulations that follow, COSTART Dictionary terminology has been used to classify reported adverse events. The stated frequencies represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. It is important to emphasize that events reported during therapy were not necessarily caused by it.
The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied.
There are no adequate and well-controlled studies examining sexual dysfunction with fluoxetine treatment.
While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.
Sarafem (Fluoxetine hydrochloride) Overdosage
Worldwide exposure to fluoxetine hydrochloride is estimated to be over 38 million patients (circa 1999). Of the 1578 cases of overdose involving fluoxetine hydrochloride, alone or with other drugs, reported from this population, there were 195 deaths.
Among 633 adult patients who overdosed on fluoxetine hydrochloride alone, 34 resulted in a fatal outcome, 378 completely recovered, and 15 patients experienced sequelae after overdosage, including abnormal accommodation, abnormal gait, confusion, unresponsiveness, nervousness, pulmonary dysfunction, vertigo, tremor, elevated blood pressure, impotence, movement disorder, and hypomania. The remaining 206 patients had an unknown outcome. The most common signs and symptoms associated with non-fatal overdosage were seizures, somnolence, nausea, tachycardia, and vomiting. The largest known ingestion of fluoxetine hydrochloride in adult patients was 8 grams in a patient who took fluoxetine alone and who subsequently recovered. However, in an adult patient who took fluoxetine alone, an ingestion as low as 520 mg has been associated with lethal outcome, but causality has not been established.
Among pediatric patients (ages 3 months to 17 years), there were 156 cases of overdose involving fluoxetine alone or in combination with other drugs. Six patients died, 127 patients completely recovered, 1 patient experienced renal failure, and 22 patients had an unknown outcome. One of the six fatalities was a 9 year-old boy who had a history of OCD, Tourette’s syndrome with tics, attention deficit disorder, and fetal alcohol syndrome. He had been receiving 100 mg of fluoxetine daily for 6 months in addition to clonidine, methylphenidate, and promethazine. Mixed-drug ingestion or other methods of suicide complicated all 6 overdoses in children that resulted in fatalities. The largest ingestion in pediatric patients was 3 grams which was non-lethal.
Other important adverse events reported with fluoxetine overdose (single or multiple drugs) include coma, delirium, ECG abnormalities (such as QT interval prolongation and ventricular tachycardia, including torsades de pointes-type arrhythmias), hypotension, mania, neuroleptic malignant syndrome-like events, pyrexia, stupor, and syncope.
Studies in animals do not provide precise or necessarily valid information about the treatment of human overdose. However, animal experiments can provide useful insights into possible treatment strategies.
The oral median lethal dose in rats and mice was found to be 452 and 248 mg/kg, respectively. Acute high oral doses produced hyperirritability and convulsions in several animal species.
Among 6 dogs purposely overdosed with oral fluoxetine, 5 experienced grand mal seizures. Seizures stopped immediately upon the bolus intravenous administration of a standard veterinary dose of diazepam. In this short-term study, the lowest plasma concentration at which a seizure occurred was only twice the maximum plasma concentration seen in humans taking 80 mg/day, chronically.
In a separate single-dose study, the ECG of dogs given high doses did not reveal prolongation of the PR, QRS, or QT intervals. Tachycardia and an increase in blood pressure were observed. Consequently, the value of the ECG in predicting cardiac toxicity is unknown. Nonetheless, the ECG should ordinarily be monitored in cases of human overdose ( Management of Overdose).
Treatment should consist of those general measures employed in the management of overdosage with any SSRI.
Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients.
Activated charcoal should be administered. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidotes for fluoxetine are known.
A specific caution involves patients who are taking or have recently taken fluoxetine and might ingest excessive quantities of a TCA. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation ( Antidepressants
, ).
Based on experience in animals, which may not be relevant to humans, fluoxetine-induced seizures that fail to remit spontaneously may respond to diazepam.
In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the .
Sarafem (Fluoxetine hydrochloride) How Supplied
Sarafem (Fluoxetine hydrochloride) (fluoxetine hydrochloride tablets) is available in 10 mg, 15 mg and 20 mg strengths.
The 10 mg tablet is a cream, round tablet embossed with S10 on one side:
0430-0210-14 - Four blister cards of 7 tablets each
The 15 mg tablet is a white, round tablet embossed with S15 on one side:
0430-0215-14 - Four blister cards of 7 tablets each
The 20 mg tablet is a yellow, round tablet embossed with S20 on one side:
0430-0220-14 - Four blister cards of 7 tablets each
________________
Store at 25˚ C (77˚ F); excursions permitted to 15˚ - 30˚ C (59˚ - 86˚ F) [see USP Controlled Room Temperature]
Sarafem (Fluoxetine hydrochloride) Animal Toxicology
Phospholipids are increased in some tissues of mice, rats, and dogs given fluoxetine chronically. This effect is reversible after cessation of fluoxetine treatment. Phospholipid accumulation in animals has been observed with many cationic amphiphilic drugs, including fenfluramine, imipramine, and ranitidine. The significance of this effect in humans is unknown.
______________________________________________________________________________
Sarafem (Fluoxetine hydrochloride) Medication Guide
Read the Medication Guide that comes with you or your family member’s antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines.
This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.
Sarafem (Fluoxetine hydrochloride)
Sarafem (Fluoxetine hydrochloride) Sarafem Carton Image - Mg
Sarafem (Fluoxetine hydrochloride) (fluoxetine hydrochloride tablets)
10 mg fluoxetine per tablet
Medication Guide to be dispensed to patients.
Usual Dose: See Package Insert.
Keep this and all drugs our of the reach of children.
Store at 25C (77F); excursions permitted to 15 - 30C (59 - 86F) [See USP Controlled Room Temperature].
See end flap for expiration date and lot number.
Sarafem (Fluoxetine hydrochloride) Sarafem Carton Image - Mg
Sarafem (Fluoxetine hydrochloride) (fluoxetine hydrochloride tablets)
15 mg fluoxetine per tablet
Medication Guide to be dispensed to patients.
Usual Dose: See Package Insert.
Keep this and all drugs our of the reach of children.
Store at 25C (77F); excursions permitted to 15 - 30C (59 - 86F) [See USP Controlled Room Temperature].
See end flap for expiration date and lot number.
Sarafem (Fluoxetine hydrochloride) Sarafem Carton Image - Mg
Sarafem (Fluoxetine hydrochloride) (fluoxetine hydrochloride tablets)
20 mg fluoxetine per tablet
Medication Guide to be dispensed to patients.
Usual Dose: See Package Insert.
Keep this and all drugs our of the reach of children.
Store at 25C (77F); excursions permitted to 15 - 30C (59 - 86F) [See USP Controlled Room Temperature].
See end flap for expiration date and lot number.
