Duloxetine; Uses, Dosage, Side Effects, Drug Interactions

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Duloxetine is a Serotonin and Norepinephrine Reuptake Inhibitor. The mechanism of action of duloxetine is as a Norepinephrine Uptake Inhibitor, and Serotonin Uptake Inhibitor.

Duloxetine is a drug which primarily targets major depressive disorder (MDD), generalized anxiety disorder (GAD), pain related to diabetic peripheral neuropathy and in some countries stress urinary incontinence (SUI). It is a thiophene derivative and a selective neurotransmitter reuptake inhibitor for serotonin, norepinephrine, and to a lesser degree dopamine. It belongs to a class of heterocyclic antidepressants known as serotonin-norepinephrine reuptake inhibitors (SNRIs) Duloxetine has not yet been FDA approved for stress urinary incontinence or for fibromyalgia. Duloxetine is a selective SNRI (selective serotonin-norepinephrine reuptake inhibitor). Duloxetine is a systemic drug therapy which affects the body as a whole.

Mechanism of Action of Duloxetine

Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors. The antidepressant and pain inhibitory actions of duloxetine are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS. The mechanism of action of duloxetine in SUI has not been determined but is thought to be associated with the potentiation of serotonin and norepinephrine activity in the spinal cord, which increases urethral closure forces and thereby reduces involuntary urine loss.

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Preclinical studies have shown that duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors in vitro. Duloxetine does not inhibit monoamine oxidase (MAO). CYMBALTA is in a class of drugs known to affect urethral resistance. If symptoms of urinary hesitation develop during treatment with CYMBALTA, consideration should be given to the possibility that they might be drug-related.

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Indications of Duloxetine

Contra-Indications of Duloxetine

  • Hypersensitivity – duloxetine is contraindicated in patients with a known hypersensitivity to duloxetine or any of the inactive ingredients.
  • Monoamine oxidase inhibitors (MAOIs) – concomitant use in patients taking MAOIs is contraindicated.
  • Uncontrolled narrow-angle glaucoma – in clinical trials, Cymbalta use was associated with an increased risk of mydriasis (dilation of the pupil); therefore, its use should be avoided in patients with uncontrolled narrow-angle glaucoma, in which mydriasis can cause sudden worsening.
  • Central nervous system (CNS) acting drugs – given the primary CNS effects of duloxetine, it should be used with caution when it is taken in combination with or substituted for other centrally acting drugs, including those with a similar mechanism of action.
  • Duloxetine and thioridazine should not be co-administered.

In addition, the FDA has reported on life-threatening drug interactions that may be possible when co-administered with triptans and other drugs acting on serotonin pathways leading to increased risk for serotonin syndrome.

Dosage of Duloxetine

Strengths: 20 mg; 30 mg; 40 mg ;60 mg;

Depression

  • Initial dose: 20 mg orally twice a day
  • dose: 60 mg per day, given either once a day or as 30 mg orally twice a day
  • Maximum dose: 120 mg orally per day
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Fibromyalgia

  • Initial dose: 30 mg orally once a day for 1 week
  • Maintenance dose: 30 to 60 mg orally once a day
  • Duration: Efficacy has been demonstrated for up to 3 months in placebo-controlled studies

Generalized Anxiety Disorder

  • Initial dose: 60 mg orally once a day
  • Maintenance dose: 60 to 120 mg orally once a day
  • Maximum dose: 120 mg orally once a day

Pain

  • Initial dose: 30 to 60 mg orally once a day
  • Maintenance dose: 60 mg orally once a day

Pediatric Generalized Anxiety Disorder

7 to 17 years

  • Initial dose: 30 mg orally once a day for 2 weeks, after which an increase to 60 mg orally once a day may be considered
  • Maintenance dose: 30 to 60 mg orally once a day
  • Maximum dose: 120 mg orally once a day
  • Duration: Episodes generally require several months or more of sustained pharmacological therapy; a periodic review of the need for ongoing maintenance treatment and appropriate dosing is recommended.

Side Effects of Duloxetine

The most common

Common

Rare

Drug Interactions of Duloxetine

Duloxetine may interact with following drugs, supplements & may change the efficacy of drugs

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Pregnancy & Lactation of Duloxetine

FDA Pregnancy Category C

Pregnancy

It has been reported that babies born to women who took medications similar to duloxetine during the last trimester of their pregnancy may experience adverse effects (such as breathing problems, seizures, trouble feeding, jitteriness, irritability, and constant crying). This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

This medication passes into breast milk. If you breastfeeding-feeding mother and are taking duloxetine, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

References

duloxetine

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