How Does Cymbalta Duloxetine Work?

Cymbalta is a drug that contains active substance known asDuloxetine, and is classified in a group of serotonin and noradrenaline reuptake inhibitors. By increasing serotonin and noradrenaline levels in the blood, Duloxetineimproves mood and symptoms of depression and anxiety. It can be bought from online pharmacy websites like Meds4sure AntiDepressants Generic Prozac Lexapro Zoloft Cymbalta Celexa Paxil Tablets which is the leading pharmacy with best prices.

In addition, Cymbalta affectsthe central nervous system pathways for pain transmission, thereby normalizing the pain tolerance threshold. Because of this effect, the drug is used to treat pain in diabetic peripheral neuropathy.

According to the FDA, Cymbalta is also indicated for the treatment of fibromyalgia and chronic musculoskeletal pain.

Pharmacokinetics of Cymbalta

Cymbalta is very well absorbed after oral administration, and maximum blood concentrations are reached 6 hours after taking the capsule. The average oral bioavailability is 50%. Food prolongs the time of achieving maximum blood concentrations, but with no clinical significance. Therefore, Cymbalta can be taken regardless of the meal.

The elimination half-life (the time for which half of the drug is excreted from the body) is from 8 to 17 hours, which means that Cymbalta retains in the body for 16-34 hours.

Cymbalta is mostly metabolized by the liver, via liver enzymes CYP2D6 and CYP1A2, and is excretedthrough the urine. Therefore, it should not be used in patients who have moderate or severe damage of liver or kidneys.

Contraindications, Precautions, and Interactions

Cymbalta is contraindicated in patients who have severe liver or kidney damage, as administration in these patients can lead to a significant increase in blood levels and serious adverse effects.

Simultaneous administration with drugs that inhibit monoamine oxidase (so-called MAO inhibitors) is strictly contraindicated due to the possible occurrence of serotonin syndrome. The most common MAO inhibitors are Isocarboxazid, Tranylcipromine, Moclobemide, Phenelzine (used to treat depression), Selegiline, Rasagiline (used to treat Parkinson’s disease), and Linezolid (an antibiotic used to treat many bacterial infections).If you have used any of the MAO inhibitors, you must wait for at least two weeks before you start taking Cymbalta.

Serotonin syndrome is a potentially dangerous, life-threatening condition. It occurs when too much serotonin is accumulated in your body. Accumulated serotonin affects the muscles, heart, brain and other organs. Symptoms of serotonin syndrome include muscle stiffness, diarrhea, confusion, irritability, disorientation, hallucinations, high blood pressure, rapid heart rate and, in severe cases, convulsions and coma.

Simultaneous administration of Cymbalta with a medicine called Fluvoxamine (a medicine used to treat depression, anxiety, and social phobia) is contraindicated. Fluvoxamine is a potent inhibitor of CYP1A2 enzyme (the enzyme through which Cymbalta is metabolized), and concomitant use may lead to an increase in Duloxetineblood levels (up to 6 times), which significantly increases the risk of side effects, including serotonin syndrome.

Concomitant use with antibiotics, such as Ciprofloxacin and Enoxacin, is also absolutely contraindicated as it increases the risk of serotonin syndrome.

Cymbalta should not be used concurrently with the following medicines because of the potential risk of serotonin syndrome:

  • Dextromethorphan – amedicine used to treat cough.
  • 5-hydroxytryptophan – a medicine used to treat obesity.
  • Opioid analgesics, such asFentanyl, Tramadol, Pentazocine, Propoxyphene, Alfentanil.
  • Tricyclic antidepressants, such as Doxepin, Amoxapine, Imipramine, Amitriptyline, Desimipramine, and Notriptylin.
  • Triptans– medicines used to treat migraine, such as Frovatriptan, Eletriptan, Almotriptan, Naratriptan, Sumatriptan and Rizatriptan.
  • Ergotamine – a medicine used to treat migraine.
  • Sertraline, Paroxetine, and Fluoxetine – medicines used to treat depression, social phobia and anxiety.
  • Buspirone– a medicine used to treat anxiety.
  • Phentermine and Fenfluramine– medicines used to treat obesity.
  • Amphetamine– a medicine used to treat attention-deficit hyperactivity disorder in children and narcolepsy.
  • Phenylpropanolamine – a medicine used to treat nasal congestion.
  • Cyclobenzaprine – a medicine used to relax muscles.

In addition, Cymbalta should not be administered concurrently with any of the following drugs:

  • Teriflunomide– a medicine used to treat relapsed forms of multiple sclerosis. Simultaneous administration increases the risk of liver damage.
  • Brexpiprazole– a medicine used to treat schizophrenia. Simultaneous administration increases the concentration of this drug in the blood, which increases the risk of low blood pressure and seizures.
  • Bupropion – a medicine used to treat severe depression and to help people quit smoking. Simultaneous administration increases the risk of seizures.
  • Panobinostat– a medicine used to treat cancers. Simultaneous administration increases the risk of bleeding.

Due to the large number of drugs that Cymbalta interacts with and the potential for serious toxic effects, it is very important that you inform your physician about all the medicines you are taking, including herbal remedies.

You should not drive or operate machinery while using Cymbalta.

Dosage Instructions

Cymbalta comes in the form of capsules, at doses of 20, 30 and 60 mg.

Severe depressive episodes

The starting dose is 60mg once a day. The dose may be increased to a maximum of 120mg per day, depending on the clinical effect. The therapeutic effect is achieved after 2-4 weeks of starting therapy.

Generalized anxiety disorder

The starting dose is 30mg once a day. The dose may be increased to a maximum of 120mg per day.

Diabetic peripheral neuropathy

The starting dose is 60mg once a day. The dosage may be increased to 120mg daily. If no effect is achieved after 2 months of therapy, the therapy should be discontinued.

Fibromyalgia&Chronic musculoskeletal pain

Therapy should start at a dose of 30mg once a day, for 7 days. After that, the dosage should be increased to 60mg once a day.

The capsule should be taken with aglass of water, regardless of the meal. Make sure you take Cymbalta capsules at the same time of day.

Sudden discontinuation of therapy should be avoided, as withdrawal symptoms may occur (suicidal thoughts, nightmares, nausea, vomiting, anxiety, agitation, hypomania, seizures, involuntary crying or laughing, paranoia, confusion and insomnia). Therefore, when discontinuing Cymbalta, the dosage should be gradually reduced over a period of 7-14 days in order to reduce the risk of withdrawal symptoms.

Side Effects

Very common side effects (occurring in more than 10% of patients) include:

  • Headache
  • Drowsiness
  • Nausea
  • Dry mouth

Common side effects (occurring in 1-10% of patients) include:

  • Decreased appetite
  • Insomnia
  • Agitation (restlessness and irritability)
  • Decreased libido
  • Disorders of orgasm
  • Erectile dysfunction
  • Ejaculation disorders
  • Abnormal dreams
  • Anxiety
  • Dizziness
  • Lethargy
  • Paresthesia
  • Tremor
  • Blurred vision
  • Ringing in the ears
  • Weight loss
  • Palpitations
  • High blood pressure
  • Hot flushes
  • Diarrhea
  • Constipation
  • Vomiting
  • Dyspepsia
  • Flatulence
  • Muscle spasms
  • Painful urination

Occasional side effects (occurring in 0.1-1% of patients) include:

  • Suicidal thoughts
  • Increase in blood sugar levels (especially in diabetics)
  • Unconsciouslygrindingof teeth
  • Apathy
  • Involuntary muscle contractions
  • Visual impairment
  • Supraventricular arrhythmias
  • Rapid heart rate
  • Tight throat feeling
  • Gastrointestinal bleeding
  • Gastroenteritis
  • Difficulty swallowing
  • Acute liverimpairment
  • Photosensitive reactions
  • Dermatitis
  • Urinary retention
  • Menstrual disorders
  • Weight gain

Rare side effects (occurring in 0.01-0.1% of patients) include:

  • Hypothyroidism
  • Anaphylactic reactions
  • Suicidal behavior
  • Hallucinations
  • Aggression
  • Serotonin syndrome
  • Glaucoma
  • Hypertensive crises
  • Hepatic insufficiency
  • Stevens-Johnson syndrome
  • Limited mouth opening
  • Galactorrhea

Call your doctor if you notice any of these side effects.

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