Duloxenta

Duloxenta (duloxetine) is an antidepressant that also has pain relief 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.

Duloxetine helps improve patients' mood, reduce anxiety, and relieve pain symptoms. However, before starting this medication, 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 diseases.
2. Chronic pain: Duloxent is also effective in reducing the 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 for the treatment of stress urinary incontinence in women.
6. Other Conditions: Duloxent may also be used for painful bladder disease, fibromyalgia, peripheral neuropathy, etc.

Release form

1. Modified-release capsules: This is the most common release form of duloxetine. The capsules contain microgranules that provide gradual release of duloxetine in the gastrointestinal tract, which promotes stable blood levels of the drug and reduces the frequency of dosing. Capsules are usually taken once or twice a day, depending on the dosage and doctor's recommendations.
2. Tablets: Although less common, duloxetine tablets may also be available in some regions. They, like capsules, can provide controlled release of the active substance.

Pharmacodynamics

1. Mechanism of action:

   • Inhibits serotonin reuptake: Duloxetine increases the level of serotonin in the synaptic space, increasing its duration of action at 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: Increased levels of serotonin and norepinephrine help improve mood and reduce symptoms of depression.
   • Anxiolytic effect: Duloxetine may help reduce anxiety and improve the condition of patients with anxiety disorders.
   • Analgesic effects: 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 2-4 weeks after starting use, although individual differences may be noticeable.
   • The analgesic effect may take longer to occur and is usually assessed after several weeks of treatment.

Pharmacokinetics

1. Absorption: Duloxetine is usually well absorbed after oral administration, regardless of food intake. Peak plasma concentrations are usually achieved 6 hours after administration.
2. Distribution: Duloxetine is highly bound to plasma proteins (about 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 mainly through cytochrome P450 (CYP) isoenzymes, mainly CYP2D6 and CYP1A2. Its main metabolites are desmethylduloxetine (also active) and desmethylduloxetine glucuronides. CYP2D6 is the main isoenzyme responsible for the formation of desmethylduloxetine.
4. Elimination: Half of duloxetine and its metabolites are eliminated through the kidneys and half through the intestines. In patients with poor renal function, dosage adjustments may be necessary.
5. Half-life: The half-life of duloxetine is approximately 12 hours, which necessitates its daily use.
6. Influence of 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 on the method of use and dosage of duloxetine:

Depression and general anxiety disorder

• Starting dose: Typically start with 60 mg once daily. In some cases, the doctor may start treatment with a lower dose to assess the patient's tolerance to the drug.
• Maintenance Dose: May vary, but is often 60 mg once daily. Depending on the patient's response and the clinical situation, the doctor may adjust the dose.
• Maximum dose: For depression, may be up to 120 mg per day, especially if lower doses are ineffective.

Fibromyalgia

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

Diabetic neuropathic pain

• Starting 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 the start of treatment.

How to take

• Duloxetine is taken by mouth, with or without food, although taking it with food may help reduce some digestive side effects.
• Capsules should be swallowed whole, without chewing, crushing, or opening, to avoid damaging the special coating designed to release the medication in a controlled manner.

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 a missed dose.
• Duloxetine should be stopped gradually, as recommended by your doctor, to avoid withdrawal symptoms.

Use Duloxenta during pregnancy

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

1. Transfer through the placenta and excretion into breast milk: Duloxetine crosses the placenta and is excreted into breast milk. No development of toxicity or other toxicities was observed in infants exposed to duloxetine during the second half of pregnancy and during breastfeeding in 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 children exposed to duloxetine in utero or while breastfeeding has not been conducted (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 dose adjusted for maternal weight, 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). It is necessary to wait at least 14 days between stopping the MAOI and starting duloxetine treatment, as this may lead to a serious or even fatal interaction known as serotonin syndrome.
3. Severe liver diseases. Duloxetine is metabolized in the liver, and its use in patients with severe hepatic impairment may result in increased toxicity.
4. Severe kidney disease. If you have severe renal failure, the use of duloxetine may be dangerous as this condition affects the elimination of the drug from the body.

Duloxetine should be used with caution in patients with:

• Bipolar disorder. Duloxetine may cause manic episodes in people with this condition.
• Angle-closure 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 an increase in blood pressure.

Side effects Duloxenta

1. Drowsiness and fatigue: Many patients report feeling drowsy or tired when starting to take 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 dry mouth when 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 an increase in blood sugar.
9. Withdrawal syndrome: When you stop taking Duloxent, withdrawal syndrome may occur, manifested by various symptoms such as dizziness, headache, insomnia, anxiety, nausea, etc.

Overdose

1. Serotonin syndrome: An overdose of duloxetine can lead to excessive levels of serotonin in the body, which can cause severe symptoms of serotonin syndrome such as hyperthermia, muscle stiffness, 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: An overdose of duloxetine may cause seizure activity and lead to epileptic seizures in some people.
4. Seizure alertness: In people with a predisposition to seizures or other neurological disorders, an overdose of duloxetine may increase seizure alertness and increase the risk of seizures.
5. Other symptoms: Other symptoms of overdose may include nausea, vomiting, drowsiness, low blood pressure, severe hyperactivity and agitation.

Interactions with other drugs

1. Liver enzyme inhibitors or inducers: Duloxetine is metabolized in the liver with the participation of cytochrome P450 enzymes (for example, CYP1A2 and CYP2D6). Drugs that are inhibitors or inducers of these enzymes may alter the blood concentration of duloxetine, which may increase or decrease its effectiveness and increase the risk of side effects.
2. Drugs that potentiate serotonergic activity: Duloxetine is a serotonin reuptake inhibitor, and concomitant use 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 bleeding 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): Concomitant use 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, hypnotics or pain relievers may increase 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: Keep Duloxent in its original packaging, away from direct sunlight and other strong light sources.
4. Accessibility for children: Keep Duloxent out of the reach of children to prevent accidental use.
5. Formulation-Specific Storage Conditions: For the liquid form of Duloxent (eg, oral solution), additional attention to storage conditions, such as temperature requirements or additional storage precautions, may be required.