Cymbalta - General Information:

Cymbalta (brand names Cymbalta, Yentreve, and in parts of Europe, Xeristar or Ariclaim) 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 manufactured and marketed by Eli Lilly and Company.
Cymbalta has not yet been FDA approved for stress urinary incontinence or for fibromyalgia.
Cymbalta is a selective SNRI (selective serotonin-norepinephrine reuptake inhibitor). Cymbalta is a systemic drug therapy which affects the body as a whole. Known also under the code name LY248686, it is a potent dual reuptake inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), possessing comparable affinities in binding to NE- and 5-HT transporter sites. It is a less potent inhibitor of dopamine reuptake.

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CymbaltaGeneric Cymbalta (Duloxetine) - 20mg 30 pills for $52.65
Cymbalta (Duloxetine) is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used to treat depression. It may also be used to treat certain types of nerve pain.


Cymbalta is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and primarily targets major depressive disorders (MDD) and stress urinary incontinence (SUI). Cymbalta is also used to treat pain and tingling caused by diabetic neuropathy (damage to nerves that can develop in people who have diabetes). Known also as LY248686, it is a potent dual inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake, possessing comparable affinities in binding to NE and 5-HT transport sites. Interestingly, its behavior contrasts to most other dual-reuptake inhibitors. Furthermore, duloxentine lacks affinity for monoamine receptors within the central nervous system.

Cymbalta for patients

Cymbalta Interactions

Potential for Other Drugs to Affect Duloxetine:

Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism.

Inhibitors of CYP1A2:
Concomitant use of duloxetine with fluvoxamine, an inhibitor of CYP1A2, results in approximately a 6-fold increase in AUC and about a 2.5-fold increase in Cmax of duloxetine. Some quinolone antibiotics would be expected to have similar effects and these combinations should be avoided.

Inhibitors of CYP2D6:
Because CYP2D6 is involved in duloxetine metabolism, concomitant use of duloxetine with potent inhibitors of CYP2D6 may result in higher concentrations of duloxetine. Paroxetine (20 mg QD) increased the concentration of duloxetine (40 mg QD) by about 60%, and greater degrees of inhibition are expected with higher doses of paroxetine. Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine).

Potential for Duloxetine to Affect Other Drugs:

Drugs Metabolized by CYP1A2:
In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity, and it is unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates.

Drugs Metabolized by CYP2D6:
Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered (at a dose of 60 mg BID) in conjunction with a single 50-mg dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold. Therefore, co-administration of Duloxetine with other drugs that are extensively metabolized by this isozyme and which have a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants [TCAs], such as nortriptyline, amitriptyline, and imipramine), phenothiazines and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution. Plasma TCA concentrations may need to be monitored and the dose of the TCA may need to be reduced if a TCA is co-administered with Duloxetine. Because of the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, Duloxetine and thioridazine should not be co-administered.

Drugs Metabolized by CYP3A:
Results of in vitro studies demonstrate that duloxetine does not inhibit or induce CYP3A activity.

Duloxetine May Have a Clinically Important Interaction with the Following Other Drugs:

When Duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, Duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

In the Duloxetine clinical trials database, three Duloxetine-treated patients had liver injury as manifested by ALT and total bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, and this may have contributed to the abnormalities seen.

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.

Potential for Interaction with Drugs that Affect Gastric Acidity:
Duloxetine has an enteric coating that resists dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. In extremely acidic conditions, Duloxetine, unprotected by the enteric coating, may undergo hydrolysis to form naphthol. Caution is advised in using Duloxetine in patients with conditions that may slow gastric emptying (e.g., some diabetics). Drugs that raise the gastrointestinal pH may lead to an earlier release of duloxetine. However, co-administration of Duloxetine with aluminum- and magnesium-containing antacids (51 mEq) or Duloxetine with famotidine, had no significant effect on the rate or extent of duloxetine absorption after administration of a 40-mg oral dose. It is unknown whether the concomitant administration of proton pump inhibitors affects duloxetine absorption.

Cymbalta Contraindications

Duloxetine is contraindicated in patients with a known hypersensitivity to duloxetine or any of the inactive ingredients.

Monoamine Oxidase Inhibitors:
Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated.

Uncontrolled Narrow-Angle Glaucoma:
In clinical trials, Duloxetine use was associated with an increased risk of mydriasis; therefore, its use should be avoided in patients with uncontrolled narrow-angle glaucoma.

Additional information about Cymbalta

Cymbalta Indication: For the treatment of major depressive disorder (MDD).
Mechanism Of Action: Cymbalta is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Cymbalta 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.
Drug Interactions: Amitriptyline Possible increase in the levels of this agent when used with duloxetine
Ciprofloxacin Ciprofloxacin increases the effect/toxicity of duloxetine
Desipramine Possible increase in the levels of this agent when used with duloxetine
Flecainide Possible increase in the levels of this agent when used with duloxetine
Fluvoxamine Fluvoxamine increases the effect and toxicity of duloxetine
Imipramine Possible increase in the levels of this agent when used with duloxetine
Isocarboxazid Possible severe adverse reaction with this combination
Nortriptyline Possible increase in the levels of this agent when used with duloxetine
Phenelzine Possible severe adverse reaction with this combination
Propafenone Possible increase in the levels of this agent when used with duloxetine
Rasagiline Possible severe adverse reaction with this combination
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Tranylcypromine Possible severe adverse reaction with this combination
Food Interactions: Take without regard to meals.
Food does not affect maximum levels reached, but delays it (from 6 to 10 hours) and total product exposure appears to be reduced by only 10%.
People taking this product who drink large amounts of alcohol are exposed to a higher risk of liver toxicity.
Generic Name: Duloxetine
Synonyms: (+-)-duloxetine; Duloxetine HCl; Duloxetine Hydrochloride
Drug Category: Adrenergic Uptake Inhibitors; Antidepressive Agents; Dopamine Uptake Inhibitors; Serotonin Uptake Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Duloxetine: Cymbalta; Yentreve;
Absorption: Orally administered duloxetine hydrochloride is well absorbed.
Toxicity (Overdose): Oral, rat LD50: 491 mg/kg for males and 279 mg/kg for females. Symptoms of overdose include tremors, convulsions, reduced activity, slow pupillary response, intermittent tremors, and rigidity.
Protein Binding: Protein binding is greater than 90%.
Biotransformation: The major biotransformation pathways for duloxetine involve oxidation of the naphthyl ring followed by conjugation and further oxidation. Both CYP2D6 and CYP1A2 catalyze the oxidation of the naphthyl ring in vitro. Metabolites found in plasma include 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate. The major circulating metabolites have not been shown to contribute significantly to the pharmacologic activity of duloxetine.
Half Life: 12 hours (range 8-17 hours)
Dosage Forms of Cymbalta: Capsule, coated pellets Oral
Chemical IUPAC Name: (3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-ylpropan-1-amine
Chemical Formula: C18H19NOS
Duloxetine on Wikipedia:
Organisms Affected: Humans and other mammals

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