Paxil

General information

Paxil is an antidepressant from the group of selective serotonin reuptake inhibitors (SSRIs). The drug is widely used to treat various mental disorders, including depression, anxiety states and some phobias. Its action is aimed at restoring the balance of serotonin in the brain, which helps to improve emotional state and reduce symptoms of psycho-emotional disorders.

Trade name

Paxil

International Nonproprietary Name (INN)

Paroxetine

Form of release

The drug is available in the following forms:

• Film-coated tablets: dosages of 10 mg, 20 mg, 30 mg, and 40 mg.
• Suspension for oral administration: concentration of 10 mg/5 ml, available in 150 ml vials.

Composition

Acting substance

Paroxetine (in the form of hemihydrate hydrochloride).

Auxiliary components

Composition depends on the form of release:

• Tablets: microcrystalline cellulose, calcium hydrophosphate, magnesium stearate, croscarmellose sodium, hypromellose (shell), titanium dioxide, polyethylene glycol.
• Suspension: purified water, sorbitol, sodium citrate, citric acid, propylparaben (preservative), orange flavoring.

Pharmacological properties

Pharmacodynamics

Paroxetine, the active ingredient of Paxil, is a potent and selective serotonin reuptake inhibitor. Its action is to block serotonin transporters (SERT) on presynaptic membranes of neurons, which leads to an increase in the concentration of this neurotransmitter in the synaptic cleft. Increased serotonin levels promote improved signal transduction between neurons, which has a positive effect on mood, reduces anxiety, and eliminates depressive symptoms.

Serotonin's effects on mood, anxiety, and depressive symptoms.

In contrast to tricyclic antidepressants, paroxetine has minimal affinity for muscarinic, histamine, and adrenergic receptors, which reduces the risk of anticholinergic and sedative side effects. However, the drug may have some stimulant effect on the central nervous system, which is sometimes manifested as anxiety or insomnia at the beginning of treatment. The therapeutic effects usually begin to appear after 1-4 weeks of regular use, although individual symptoms such as anxiety may decrease sooner.

Paroxetine also demonstrates efficacy in the treatment of conditions associated with dysregulation of the serotoninergic system, such as obsessive-compulsive disorder and panic attacks. Its action is not accompanied by a marked effect on norepinephrine or dopamine, making its profile more specific than other antidepressants.

Pharmacokinetics

Paroxetine is well absorbed from the gastrointestinal tract after oral administration, with food intake having no significant effect on the rate or extent of absorption. Maximum concentration in blood plasma is reached in 2-8 hours, depending on the individual characteristics of the patient and the form of release. Bioavailability is about 50% due to the effect of first passage through the liver, where the drug undergoes intensive metabolism.

Binding to plasma proteins (mainly albumin) reaches 95%, which ensures stable distribution of the substance in the body. The volume of distribution is about 13-28 l/kg, which indicates penetration of paroxetine into tissues, including the brain. Metabolism occurs in the liver with the participation of enzymes of the cytochrome P450 system, mainly CYP2D6 isoenzyme. The main metabolites (glucuronic and sulfuric acid conjugates) are pharmacologically inactive.

The elimination half-life of paroxetine ranges from 16 to 24 hours in most patients, but may increase with hepatic or renal dysfunction. Excretion is primarily through the kidneys (about 64% as metabolites) and partially through the intestine (about 36%). In elderly patients or persons with slow metabolism accumulation of the drug is possible, which requires dosage adjustment.

Indications for use

Paxil is indicated for the following diseases and conditions:

• Major depressive disorder (including recurrent depression).
• Obsessive-compulsive disorder (OCD).
• Panic disorder (with or without agoraphobia).
• Social anxiety disorder (social phobia).
• Generalized anxiety disorder (GAD).
• Posttraumatic stress disorder (PTSD).
• Perimenstrual dysphoric disorder (in some cases, as prescribed by a physician).

Contraindications

The use of Paxil is prohibited under the following conditions:

• Excessive sensitivity to paroxetine or any of the excipients.
• Simultaneous use of monoamine oxidase inhibitors (MAOIs) or a period of less than 14 days after their withdrawal.
• Combined use with thioridazine or pimozide due to risk of QT interval prolongation and arrhythmias.
• Severe renal impairment (creatinine clearance less than 30 mL/min) without dose adjustment.
• Severe hepatic insufficiency.
• Childhood under 7 years of age (for suspension) or under 18 years of age (for certain indications such as depression).
• Unstable epilepsy.

Method of administration and dosage

How to take

The drug is taken orally, preferably in the morning, regardless of meals. Tablets should be swallowed whole, drinking enough water (100-150 ml). The suspension should be shaken before use, measure the required dose using a measuring cup or syringe and drink water.

Dosages for adults and children

Adults

The starting dose depends on the indication:

• Depression: 20 mg once daily, increasing by 10 mg every 1 to 2 weeks as needed to a maximum dose of 50 mg daily.
• OCP: 20 mg once daily, with possible increase to 40-60 mg daily.
• Panic disorder: 10 mg daily, with gradual increases to 40 mg (maximum 60 mg).
• Social phobia, GTR, PTSD: 20 mg daily, with a maximum of 50 mg.

Children (7-17 years of age, suspension only)

Use limited to OCD and social phobia: starting dose 10 mg daily, increasing by 10 mg every 1-2 weeks to a maximum dose of 40 mg daily.

Dose adjustment for certain conditions

In moderate renal or hepatic impairment, the starting dose is reduced to 10 mg daily, with a maximum dose of 40 mg. In elderly patients, it is recommended to start at 10 mg per day, not to exceed 40 mg. In case of CYP2D6 dysfunction (slow metabolism) the dose is also adjusted downward.

Side effects

The following adverse reactions are possible when taking Paxil:

• Side of the nervous system: headache, dizziness, insomnia, drowsiness, tremor, anxiety.
• Side of the digestive system: nausea, dry mouth, diarrhea, constipation, decreased appetite.
• Cardiovascular system: tachycardia, slight increase in blood pressure.
• Reproductive system: decreased libido, erectile dysfunction, delayed ejaculation.
• Skin reactions: increased sweating, rash, itching.
• Other: fatigue, weight gain, withdrawal syndrome in case of abrupt discontinuation of intake.

Overdose

Symptoms of overdose

An overdose may be observed:

• Nausea, vomiting, diarrhea.
• Sleepiness or agitation.
• Tachycardia, tremor, seizures.
• Serotonin syndrome (fever, confusion, muscle rigidity).
• Rarely: coma or respiratory arrest.

First aid measures

In case of overdose it is necessary:

1. Stop taking the drug.
2. Seek medical attention.
3. Rinse the stomach (if it has been less than 1 hour).
4. Give activated charcoal (1 g/kg body weight).
5. Control vital functions until a doctor arrives.

Interaction with other drugs

Influence on the effects of other drugs

Paxil may increase the effects of:

• Tricyclic antidepressants and other SSRIs (risk of serotonin syndrome).
• Anticoagulants (increased risk of bleeding).
• Anticonvulsants (lowering the threshold for seizure activity).

The drug inhibits CYP2D6, which may increase the concentration of drugs such as tamoxifen, risperidone, and metoprolol.

Compatibility with alcohol and food

Alcohol enhances sedation and increases the risk of side effects, so its use is not recommended. Food does not affect the absorption of the drug.

Special instructions

Use in pregnancy and breastfeeding

Paxil is used in pregnancy only if absolutely necessary, as paroxetine may increase the risk of congenital heart defects in the fetus (especially in the first trimester). The drug is excreted with breast milk, so during lactation its use is contraindicated or requires temporary cessation of breastfeeding.

Effects on driving and mechanisms

The drug may cause drowsiness, dizziness or decreased concentration, especially during the first weeks of administration. Patients should refrain from driving until individual reaction is evaluated.

Particularities of use in the elderly and children

Elderly patients are more likely to experience side effects such as hyponatremia, so electrolyte monitoring and dose reduction are required. In children and adolescents (under 18 years of age), the drug increases the risk of suicidal ideation, which requires careful observation at the beginning of treatment.