Sarafem

Name: Sarafem

What other information should I know?

Keep all appointments with your doctor.

Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are taking fluoxetine.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

What is fluoxetine, and how does it work (mechanism of action)?

Fluoxetine is an oral drug that is used primarily for treating depression. It is in a class of drugs called selective serotonin reuptake inhibitors (SSRIs), a class that includes citalopram (Celexa), paroxetine (Paxil) and sertraline (Zoloft). Fluoxetine affects neurotransmitters, the chemicals that nerves within the brain use to communicate with each other. Neurotransmitters are manufactured and released by nerves and then travel and attach to nearby nerves. Thus, neurotransmitters can be thought of as the communication system of the brain. Serotonin is one neurotransmitter that is released by nerves in the brain. The serotonin either travels across the space between nerves and attaches to receptors on the surface of nearby nerves or it attaches to receptors on the surface of the nerve that produced it, to be taken up by the nerve and released again (a process referred to as re-uptake). Many experts believe that an imbalance among neurotransmitters is the cause of depression. Fluoxetine works by preventing the reuptake of one neurotransmitter, serotonin, by nerve cells after it has been released. Since uptake is an important mechanism for removing released neurotransmitters and terminating their actions on adjacent nerves, the reduced uptake caused by fluoxetine increases free serotonin that stimulates nerve cells in the brain. The FDA approved Fluoxetine in December 1987.

Indications

Premenstrual Dysphoric Disorder (PMDD)

SARAFEM is indicated for the treatment of premenstrual dysphoric disorder (PMDD) [see Clinical Studies].

The effectiveness of SARAFEM in long-term use (that is, for more than 6 months) has not been systematically evaluated in placebo-controlled trials. The use of SARAFEM for extended periods should be periodically re-evaluated for the individual patient [see DOSAGE AND ADMINISTRATION].

Overdose

Human Experience

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 nonlethal.

Other important adverse reactions 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 reactions, pyrexia, stupor, and syncope.

Animal Experience

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 [see DRUG INTERACTIONS].

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 Physicians' Desk Reference (PDR).

Side Effects of Sarafem

Sarafem may cause serious side effects. See "Drug Precautions" section.

Common possible side effects in people who take Sarafem include: 

  • headache
  • pain
  • diarrhea
  • sexual problems (decrease in desire)
  • diarrhea
  • weakness
  • feeling tired or fatigued 
  • change in sleep habits, including insomnia
  • sinus infection or sore throat 
  • dizziness
  • anxiety and/or nervousness
 Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Sarafem. For more information, ask your healthcare provider or pharmacist.

Other Requirements

  • Store Sarafem at 77°F (25°C). 
  • Keep Sarafem and all medicines out of the reach of children.

Sarafem (fluoxetine) side effects

Get emergency medical help if you have signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

  • blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;

  • high levels of serotonin in the body--agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting;

  • low levels of sodium in the body--headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;

  • severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out; or

  • severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

  • sleep problems (insomnia), strange dreams;

  • headache, dizziness, vision changes;

  • tremors or shaking, feeling anxious or nervous;

  • pain, weakness, yawning, tired feeling;

  • upset stomach, loss of appetite, nausea, vomiting, diarrhea;

  • dry mouth, sweating, hot flashes;

  • changes in weight or appetite;

  • stuffy nose, sinus pain, sore throat, flu symptoms; or

  • decreased sex drive, impotence, or difficulty having an orgasm.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What do I need to tell my doctor BEFORE I take Sarafem?

  • If you have an allergy to fluoxetine or any other part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking any of these drugs: Linezolid or methylene blue.
  • If you are taking pimozide.
  • If you are taking thioridazine.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking Sarafem within 14 days of those drugs can cause very bad high blood pressure.
  • If you are breast-feeding. Do not breast-feed while you take this medicine.

This is not a list of all drugs or health problems that interact with Sarafem.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some other side effects of Sarafem?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Upset stomach.
  • Dry mouth.
  • Feeling sleepy.
  • Loose stools (diarrhea).
  • Strange or odd dreams.
  • Not able to sleep.
  • Feeling tired or weak.
  • Flu-like signs.
  • Yawning.
  • Hot flashes.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Indications and Usage for Sarafem

Sarafem 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 (see CLINICAL 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 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 for extended periods should periodically reevaluate the long–term usefulness of the drug for the individual patient.

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