Duloxenta

Duloxent (duloxetine) is an antidepressant that also has pain-relieving properties. It belongs to a class of drugs known as selective serotonin and norepinephrine reuptake inhibitors (SNRIs). Duloxetine is used to treat a variety of conditions, including depression, anxiety disorders, chronic pain, and neuropathic pain.

Duloxent helps improve patients' mood, reduce anxiety, and relieve pain symptoms. However, before starting to take this drug, it is important to consult with your doctor to determine the appropriate dosage and assess the indications for use in your particular case.

Indications Duloxenta

1. Depressive disorders: Duloxent is widely used in the treatment of depression of varying severity, including major depressive disorder, dysthymia (chronic low depression) and depression associated with other mental and somatic illnesses.
2. Chronic pain: Duloxent is also effective in reducing symptoms of chronic pain. This may include osteoarthritis pain, chronic back pain, neuropathic pain (such as diabetic neuropathy), migraines, and fibromyalgia.
3. Obsessive-compulsive disorder (OCD): Duloxent may be used as an adjunctive treatment for OCD.
4. Generalized Anxiety Disorder (GAD): The drug may be used to reduce the symptoms of GAD.
5. Stress urinary incontinence: In some cases, Duloxent may be recommended to treat stress urinary incontinence in women.
6. Other conditions: Duloxent can also be used for painful bladder disease, fibromyalgia, peripheral neuropathy, etc.

Release form

1. Modified-release capsules: This is the most common form of duloxetine. The capsules contain microbeads that provide a gradual release of duloxetine in the gastrointestinal tract, which helps maintain stable blood levels and reduces the frequency of dosing. The capsules are usually taken once or twice a day, depending on the dosage and your doctor’s recommendations.
2. Tablets: Although less common, duloxetine tablets may also be available in some areas. These, like capsules, can provide controlled release of the active ingredient.

Pharmacodynamics

1. Mechanism of action:

   • Inhibits serotonin reuptake: Duloxetine increases the level of serotonin in the synaptic space, increasing its duration of action on postsynaptic receptors. This helps improve mood and reduce symptoms of depression.
   • Inhibits norepinephrine reuptake: Duloxetine also increases norepinephrine levels, which may help improve mood, increase energy, and reduce anxiety.

2. Pharmacological effects:

   • Antidepressant effect: Increasing levels of serotonin and norepinephrine helps improve mood and reduce symptoms of depression.
   • Anxiolytic action: Duloxetine may help reduce anxiety and improve the condition of patients with anxiety disorders.
   • Analgesic action: Duloxetine is also used to treat chronic pain, as increasing serotonin and norepinephrine levels can modulate pain perception and improve pain control.

3. Time until effect appears:

   • Improvements in mood and reduction in depressive symptoms usually occur within 2-4 weeks of starting treatment, although individual differences may be noticeable.
   • The analgesic effect may take longer to develop and is usually assessed after several weeks of treatment.

Pharmacokinetics

1. Absorption: Duloxetine is generally well absorbed after oral administration, regardless of food intake. Peak plasma concentrations are usually reached 6 hours after administration.
2. Distribution: Duloxetine is highly bound to plasma proteins (approximately 90%), mainly to albumin. It has a large volume of distribution, indicating its distribution in many tissues of the body.
3. Metabolism: Duloxetine is metabolized in the liver primarily via cytochrome P450 (CYP) isoenzymes, primarily CYP2D6 and CYP1A2. Its major metabolites are desmethylduloxetine (also active) and desmethylduloxetine glucuronides. CYP2D6 is the major isoenzyme responsible for the formation of desmethylduloxetine.
4. Elimination: Half of duloxetine and its metabolites are excreted via the kidneys and half via the faeces. In patients with poor renal function, dosage adjustments may be necessary.
5. Half-life: The half-life of duloxetine is approximately 12 hours, allowing for daily use.
6. Influencing factors: The pharmacokinetics of duloxetine may be altered in the elderly, in patients with poor liver or kidney function, and in those taking other drugs that affect CYP2D6 and CYP1A2.

Dosing and administration

Basic recommendations for the method of administration and dosage of duloxetine:

Depression and Generalized Anxiety Disorder

• Initial dose: Usually starts with 60 mg once daily. In some cases, the doctor may start treatment with a lower dose to assess the patient's tolerability.
• Maintenance dose: May vary, but is often 60 mg once daily. Depending on the patient's response and clinical situation, the doctor may adjust the dose.
• Maximum dose: For depression, it may be as high as 120 mg per day, especially if lower doses are not effective enough.

Fibromyalgia

• Initial dose: Usually start with 30 mg per day for one week.
• Maintenance dose: Usually 60 mg daily. Depending on tolerability and clinical response, the dose may be increased or decreased.

Diabetic neuropathic pain

• Initial dose: 60 mg once daily. Some studies suggest that starting treatment with 30 mg for the first week may help reduce side effects associated with starting treatment.

Method of administration

• Duloxetine is taken by mouth with or without food, although taking it with food may help reduce some digestive side effects.
• The capsules should be swallowed whole, without chewing, crushing or opening, to avoid damaging the special coating designed to provide controlled release of the drug.

Important precautions

• If you miss a dose, take it as soon as possible, but if it is almost time for your next dose, skip the missed dose and continue with your normal schedule. Do not double the dose to make up for the missed one.
• Discontinuation of duloxetine should be done gradually according to the schedule recommended by the doctor to avoid withdrawal symptoms.

Use Duloxenta during pregnancy

The use of Duloxent during pregnancy may pose potential risks and should be done with caution.

1. Placental transfer and excretion in breast milk: Duloxetine crosses the placenta and is excreted in breast milk. No developmental toxicity or other toxicity was observed in infants exposed to duloxetine during the second half of pregnancy and during breastfeeding for the first 32 days after birth. However, the possibility of functional/neurobehavioral deficits manifesting later in life cannot be excluded, as long-term follow-up of infants exposed to duloxetine in utero or during breastfeeding has not been performed (Briggs et al., 2009).
2. Risk of spontaneous abortion and other outcomes: Use of duloxetine during pregnancy is associated with an increased risk of spontaneous abortion, but not with an increased risk of other adverse outcomes such as major birth defects. Exposure during late pregnancy may be associated with poor neonatal adjustment, but the extent of this risk is unknown. Exposure of duloxetine in breast milk is less than 1% of the maternal weight-adjusted dose, suggesting that duloxetine can be safely used by women who are breastfeeding (Andrade, 2014).

Contraindications

1. Individual hypersensitivity to duloxetine or any other component of the drug.
2. Concomitant use with monoamine oxidase inhibitors (MAOIs): A minimum of 14 days should be observed between stopping the MAOI and starting treatment with duloxetine, as this may result in a serious or even fatal interaction known as serotonin syndrome.
3. Severe liver disease. Duloxetine is metabolized in the liver and its use in patients with severe liver dysfunction may result in increased toxicity.
4. Severe kidney disease. If you have severe kidney failure, using duloxetine can be dangerous because this condition affects how the drug is eliminated from the body.

Duloxetine should be used with caution in patients with:

• Bipolar disorder. Duloxetine can cause a manic reversal in people with this disorder.
• Closed-angle glaucoma. The drug may cause an increase in intraocular pressure.
• Bleeding or bleeding disorders. Duloxetine may increase the risk of bleeding.
• High blood pressure. Duloxetine may cause high blood pressure.

Side effects Duloxenta

1. Drowsiness and fatigue: Many patients report feeling drowsy or tired when they first start taking Duloxent. This side effect usually decreases over time.
2. Dizziness: This is one of the most common side effects of antidepressants, including Duloxent.
3. Dry mouth: Some people may experience a feeling of dry mouth while taking Duloxent.
4. Sleep problems: This may include insomnia or changes in dreams.
5. Loss of appetite or weight gain: Some patients may experience loss of appetite, while others may experience weight gain.
6. Ejaculatory delay or sexual dysfunction: These side effects may affect sexual function in some patients.
7. Increased blood pressure: Taking Duloxent may cause increased blood pressure in some people.
8. Increased blood sugar: People with diabetes or a predisposition to diabetes may experience increased blood sugar levels.
9. Withdrawal Syndrome: When you stop taking Duloxent, withdrawal syndrome may occur, which can include various symptoms such as dizziness, headache, insomnia, anxiety, nausea, etc.

Overdose

1. Serotonin syndrome: Overdosing on duloxetine can result in excessive levels of serotonin in the body, which can cause serious symptoms of serotonin syndrome, such as hyperthermia, muscle rigidity, hyperreflexia, shaking, loss of consciousness, and even death.
2. Tachycardia and arrhythmias: Excessive effects of duloxetine on the serotonin and noradrenergic systems may cause cardiac arrhythmias and tachycardia, which increases the risk of cardiovascular complications.
3. Seizures and convulsions: Overdosing on duloxetine may cause seizure activity and lead to epileptic seizures in some people.
4. Seizure Predisposition: In people with a predisposition to seizures or other neurological disorders, overdose of duloxetine may increase seizure predisposition and increase the risk of seizures.
5. Other symptoms: Other symptoms of overdose may include nausea, vomiting, drowsiness, decreased blood pressure, severe hyperactivity and agitation.

Interactions with other drugs

1. Inhibitors or inducers of liver enzymes: Duloxetine is metabolized in the liver by cytochrome P450 enzymes (eg, CYP1A2 and CYP2D6). Drugs that are inhibitors or inducers of these enzymes may alter the concentration of duloxetine in the blood, which may increase or decrease its effectiveness and increase the risk of side effects.
2. Drugs that enhance serotonergic activity: Duloxetine is a serotonin reuptake inhibitor, and co-administration with other drugs such as selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, or triptans may increase the risk of developing serotonin syndrome.
3. Drugs that increase hemorrhagic risks: Duloxetine may increase the risk of bleeding when used in combination with anticoagulants, antiplatelet agents, NSAIDs and other drugs that affect the blood coagulation system.
4. Drugs that affect the electrocardiogram (ECG): Coadministration of duloxetine with drugs that prolong the QT interval or cause arrhythmias may increase the risk of cardiac complications.
5. Drugs that increase the risk of hyponatremia: Duloxetine may increase the risk of hyponatremia, especially when used concomitantly with diuretics or other drugs that increase sodium excretion.
6. Drugs affecting the central nervous system: Concomitant use of duloxetine with alcohol, sleeping pills, or pain relievers may enhance their sedative effect.

Storage conditions

1. Temperature: Store Duloxent at room temperature between 15 and 30 degrees Celsius. Avoid overheating or freezing the drug.
2. Humidity: Keep Duloxent in a dry place. Avoid storing in the bathroom or near a sink where there is high humidity.
3. Light: Store Duloxent in its original package, away from direct sunlight and other sources of bright light.
4. Child safety: Keep Duloxent out of reach of children to prevent accidental ingestion.
5. Storage conditions for a specific form: In the case of a liquid form of Duloxent (eg, oral solution), additional attention to storage conditions, such as temperature requirements or additional storage precautions, may be required.