Depreta

Depreta - Uses | Pharmacokinetics | Effects

Depreta is a medicine that contains duloxetine as an active substance. It works by enhancing serotonergic and noradrenergic activity in the body, and it is assumed that this mechanism leads to antidepressant, anxiolytic and analgesic effects. It belongs to the family of medicines called serotonin and noradrenaline inhibitors (SNRI).

Depreta does not have clinically significant affinity for opioid, histamine, adrenergic and dopamine receptors.

Uses

Depreta is used to treat

  • Generalized anxiety disorder (symptoms include restlessness, insomnia, muscle tension, irritability, nervousness, and gastrointestinal disturbances).
  • Episodes of major depression (symptoms include lack of pleasure in activities you usually enjoyed before the onset of the depression, lack of energy, fatigue, feelings of guilt, low self-esteem, impaired concentration, decreased attention, suicidal thoughts, headache and dizziness).
  • Diabetic peripheral neuropathy (burning sensation, tingling sensation and pain).
  • Chronic pain that affects muscles and bones
  • Fibromyalgia (symptoms include chronic pain in the muscles, exhaustion, headache, migraine, dry mouth, constipation and neck stiffness).

Pharmacokinetics

The elimination half-life of this drug is 8-17 hours depending on the dose. Maximum plasma concentration is reached within 6 hours after taking the capsule (if taken on an empty stomach) or after 10 hours if taken during or after a meal.

More than 90% of this medication binds to plasma proteins, mainly for albumin and alpha-1 acid glycoprotein. The main metabolic pathway of Depreta includes oxidation process, and the main catalysts for this process are CYP2D6 and CYP1A2 enzymes. The main metabolites of the Depreta include:

  • 4-hydroxy-duloxetine-glucuronide
  • 5-hydroxy-6-methoxy-duloxetine-sulphate.

The largest part (70%) of the drug is excreted through the urine, while 20% is excreted through the faeces.

Contraindications and precautions

Contraindications for the use of Depreta are as follows:

  • Known hypersensitivity to the active substance duloxetine.
  • Open angle glaucoma.
  • Concomitant use with medicines known as MAO inhibitors, such as: selegiline (used to treat Parkinson's disease), linezolid (antibiotic), moclobemide, tranylcypromine and isocarboxazide (antidepressants). Simultaneous administration with these medicines can lead to the serotonin syndrome - a condition that can be life-threatening.

Patients who have a history of suicidal thoughts must use this medicine with extra precaution. If you notice suicidal thoughts or ideas, contact your doctor immediately.

Depreta can reduce plasma concentration of sodium and patients who already have hyponatraemia, should not use this medicine without medical supervision.

Cases of fatal hepatic insufficiency have been reported in patients treated with this medicine. For this reason, periodic monitoring of liver function while using Depreta is recommended.

Patients on anticoagulant therapy must cautiously apply Depreta due to an increased risk of bleeding.

Patients who have a history of convulsions must notify the physician prior starting this medicine.

Depreta can increase blood glucose and cholesterol levels. It also may exacerbate symptoms in patients with urinary incontinence.

Depression, Pregnancy and Breastfeeding

FDA pregnancy category C. Clinical studies have shown toxic effects on embryonic, fetal and postnatal development, and Depreta should not be used during pregnancy unless necessary.

Avoid breastfeeding while taking this medicine.

Dosage

The recommended dosage is given in the table below:

Indications Dosage instructions
Generalized anxiety disorder

Initial dose: 30 - 60 mg, depending on the severity of the condition and general health status of the patient.

The usual maintenance dose: 60 mg once a day.

Maximum daily dose: 120 mg.

Episodes of major depression

Initial dose: 20 - 30 mg, twice daily.

Maintenance dose: 30 mg twice daily or 60 mg once daily.

Maximum daily dose: 120 mg.

Chronic pain that affects muscles and bones

Initial dose: 30 mg once a day.

Maintenance dose: 30 mg twice daily.

Maximum daily dose: 60 mg.

Diabetic peripheral neuropathy 60 mg once daily
Fibromyalgia 30 mg once daily for the first 7 days, and then 60 mg as a single dose or divided into two doses.

The therapeutic response usually occurs after 2-4 weeks of therapy.

Interactions

Symptoms of serotonin syndrome include: diarrhea, excessive sweating, hallucinations, tachycardia, and high blood pressure. Serotonin syndrome may have a fatal outcome!

Concomitant use with the following drugs increases the risk of serotonin syndrome:

  • Fentanyl and pentazocine (opioid analgesics).
  • Dextromethorphan (a potent antitussive).
  • Triptans - medicines used to treat migraine (e.g. almotriptan, sumatriptan, rizatriptan, frovatriptan and zolmitriptan).
  • Palonosetron, dolasetron, ondansetron and granisetron - medicines used to relieve the nausea that occurs associated with chemotherapy.
  • Selective serotonin uptake inhibitors, such as: selegiline, fluoxetine, paroxetine, fluvoxamine, and others.
  • Tricyclic antidepressants.
  • MAO inhibitors
  • Buspirone - anxiolytic.

Concomitant use with the following drugs should also be avoided:

  • Phenylpropanolamine (a medicine used to treat nasal congestion and used in numerous cold medications). Depreta increases the concentration of phenylpropalomine in the blood, therefore increases the risk of nervousness and anxiety.
  • Bupropion - antidepressant. Concomitant administration with this medicine increases the risk of convulsions.

Side effects

The most common side effects of this medicine are nausea, vomiting, dizziness and fatigue.

In addition, Depreta can cause the following adverse reactions:

  • Dry mouth
  • Hyperhidrosis
  • Insomnia
  • Loss of consciousness
  • Hypersensitivity
  • Anaphylactic reaction
  • Bruxism
  • Suicidal ideas
  • Disorders of orgasm
  • Disorientation
  • Myoclonus
  • Convulsions
  • Blurred vision
  • Hypertension
  • Tachycardia
  • Orthostatic hypotension, syncope and somnolence
  • Hepatic failure
  • Urinary retention
  • Hyperprolactinaemia
  • Excessive sweating and increased thirst

References

  1. PIL
  2. FDA