Fluoxetine

BRAND NAMES:

Sarafem-It contains the active ingredients of fluoxetine. It is available in the form of tablets used to treat depression.

Symbyax- It contains the active ingredients of fluoxetine. It is available in the form of capsules and tablets with a combination of Olanzapine and Fluoxetine used to treat depression.

Prozac –It contains the active ingredients of fluoxetine. It is available in the form of capsules used to treat depression.

MECHANISM OF ACTION:

Fluoxetine exerts its anti-depressant effects by blocking the reuptake of serotonin in the presynaptic serotonin neurons by blocking the reuptake transporter protein in the presynaptic terminal. Fluoxetine also has mild activity at the 5-HT2A and 5-HT2C receptors. It has a minimal activity on noradrenergic reuptake. Due to the drug's action on the reuptake of serotonin, fluoxetine produces an activating effect, and due to its long half-life, the initial anti-depressant effect emerges within 2 to 4 weeks.

PHARMACOKINETICS:

Absorption: Peak plasma concentrations of fluoxetine are attained after 6 to 8 hours. Fluoxetine is well absorbed with a bioavailability of 70% to 90%. Food does not appear to impact the bioavailability of fluoxetine, but it may slow its absorption by 1 to 2 hours, which is not clinically significant. Fluoxetine may be administered with or without food.

Distribution: Between 20 and 42 L/kg is the range of the volume of distribution of fluoxetine and its metabolite.

Metabolism: Fluoxetine’s active metabolite is nor-fluoxetine produced when the cytochrome P450 enzyme acts on it. Prescribers must remember that fluoxetine has several drug-drug interactions due to its metabolism through the CYP3A4. Fluoxetine has a half-life of 2 to 4 days, and its active metabolite nor-fluoxetine has a half-life of 7 to 9 days. Approximately 7% of individuals definitively exhibit poor metabolism of fluoxetine due to reduced activity of CYP2D6.

Excretion: The metabolism of fluoxetine is extensively resulting in approximately 2.5% of the administered dose being excreted unchanged in the urine.

PHARMACODYNAMICS:

When compared to earlier developed classes of anti-depressants like tricyclic anti-depressants, fluoxetine has a far more desirable adverse effect profile because it binds to 5-HT, dopaminergic, adrenergic, cholinergic, muscarinic, and histamine receptors with relatively poor affinity

DOASAGE AND ADMINISTRATION:

Fluoxetine is available as Prozac and generic fluoxetine in the following dosage forms that are taken orally

• 10mg, 20mg, 40mg of oral capsules

• 90mg of delayed-release oral capsules

• 20 mg/5ml oral solution

• 10mg, 20mg, and 60mg oral tablets.

Fluoxetine should be administered once a day, either in the morning or evening, and started at 20mg daily. It is only available in an oral formulation as an oral solution, tablet, capsule, and delayed-release capsule.

It is also available in a fixed dose combination with Olanzapine.

DRUG INTERACTIONS:

Drug interaction with fluoxetine includes

• Tryptophan

• Blood thinner- Warfarin

• Mental illness- amitriptyline, Buspirone, Desipramine and Lithium

• Migraine headache medicine- rizatriptan, sumatriptan and zolmitriptan

• Narcotic pain medicine- Fentanyl, Tramadol

CONTRAINDICATIONS:

Contraindications of fluoxetine include hypersensitivity to fluoxetine or any component in its formulation. This drug is also contraindicated with the concurrent use of monoamine oxidase inhibitors due to the risk of serotonin syndrome. Never initiate fluoxetine in a patient receiving linezolid. Use this agent with caution in those with a history of seizures or older patients.

SIDE EFFECTS:

Fluoxetine may cause serious side effects including

• Blurred vision

• Pounding heartbeat

• Dizziness

• Shortness of breath

Low levels of sodium in the body

• Headache

• Confusion

• Slurred speech 

• Severe weakness

• Vomiting

Severe nervous system reaction

• Stiff muscle

• Hugh fever

• Sweating

• Confusion

• Uneven heartbeat

Symptoms of serotonin syndrome

• Agitation

• Hallucinations

• Fever

• Fast heartbeat

• Nausea

• Vomiting

• diarrhea

OVERDOSE:

In the case of SSRI overdose, the goal is to provide supportive therapy. Thus support can be in the form of airway protection, serial ECGs to monitor for cardiotoxicity, administration of benzodiazepines for sedation, and GI decontamination with activated charcoal. Serotonin syndrome is treated with the administration of cyproheptadine. 

TOXICITY:

In rare cases, a monotherapy overdose of fluoxetine is fatal. When combined with alcohol, it may result in respiratory depression and ataxia. When the medication is taken in excess or in combination with other substances that raise serotonin levels, it may result in serotonin syndrome. 

STORAGE:

Place in a firmly sealed container in a cold, dry place. Avoid the sun. The suggested temperature range for fluoxetine is 68°F to 77°F (20°C to 25°C). During transportation, the temperature can vary between 59°F and 86°F (15°C and 30°C) for a length of time.