Reagila

Reagila (cariprazine) is a medication used to treat schizophrenia in adults and to treat bipolar disorder in adults and children aged 10 years and older. It is an atypical antipsychotic that works by changing the activity of neurotransmitters in the brain, such as dopamine and serotonin. Reagila may help improve symptoms of schizophrenia, such as delusions, hallucinations, dissociated thoughts, and apathy, as well as symptoms of bipolar disorder, such as mania and depression. Like any medicine, Reagila can cause side effects, so it is important to take it under the supervision of a doctor and follow his or her instructions.

Indications Reagils

1. Schizophrenia: Reagila is used to improve symptoms of schizophrenia, including delusions, hallucinations, dissociated thoughts, and decreased emotional and social functioning.
2. Bipolar disorder: This medication may be used to manage the symptoms of bipolar disorder, including mania (elevated mood, increased energy and activity, aggression) and depression (low mood, loss of interest in usual activities, sleepiness).

Release form

Reagila is usually available as a tablet to take by mouth.

Pharmacodynamics

1. Dopamine receptor antagonism: Reagila is a dopamine D2 and D3 receptor antagonist. This means that it blocks the action of dopamine, a neurotransmitter associated with the onset of psychosis. Dopamine receptor antagonism helps reduce the positive symptoms of schizophrenia, such as hallucinations and delusions.
2. Partial serotonin receptor agonism: M has a partial agonist effect on serotonin 5-HT1A receptors. This may improve mood and may also help manage the depressive symptoms associated with bipolar disorder.
3. Modulation of the glutamate system: Reagila also affects the glutamate system by modulating the activity of NMDA receptors. Glutamate is a key excitatory neurotransmitter in the central nervous system, and its role in the pathophysiology of mental disorders is still being studied. Modulation of the glutamate system may improve cognitive function and help reduce the negative symptoms of schizophrenia.
4. Minimal effects on other receptors: Reagila is generally well tolerated and is associated with fewer side effects related to histaminergic, muscarinic and α1-adrenergic receptor antagonism.

Pharmacokinetics

1. Absorption: Reagila is generally well absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations are usually reached approximately 1-3 hours after administration.
2. Distribution: Reagila is highly bound to plasma proteins (approximately 91-98%), mainly to albumin. It has a large volume of distribution, indicating widespread distribution in body tissues.
3. Metabolism: Reagila is metabolized in the liver by cytochrome P450 enzymes, primarily by the CYP3A4 isoenzyme. The major metabolite of cariprazine, desmethylcariprazine, is also active.
4. Excretion: About 26% of the cariprazine dose is excreted in the urine, mainly as metabolites, and the remainder in the faeces.
5. Half-life: The half-life of Reagila is approximately 2-3 days after daily administration.
6. Food: Food intake may increase the area under the plasma concentration curve (AUC) of Reagila and the maximum concentration (Cmax), but this usually does not have a clinically significant effect on its efficacy.
7. Individual characteristics: The pharmacokinetics of Reagila may vary in different patients depending on factors such as age, gender, the presence of liver or kidney pathologies, and the use of other medications.
8. Interactions: Reagila may interact with other drugs, especially other psychotropic drugs, and this may affect its pharmacokinetics and/or pharmacodynamics.

Dosing and administration

1. Dosage:

   • The usual starting dose of Reagila for the treatment of schizophrenia is 1.5 mg once daily. The dose may be increased to 3 mg once daily after a few days, taking into account the patient's response to treatment.
   • For the treatment of bipolar disorder, the starting dose is usually 0.5 mg once daily. The dose may be increased to 1.5 mg or 3 mg depending on the patient's response to treatment.

2. Directions for use:

   • Reagila tablets are usually taken orally, regardless of food intake.
   • The tablets should be swallowed whole, without chewing or breaking them.
   • It is recommended to take Reagila every day at the same time to maintain a stable level of the drug in the body.

3. Duration of treatment:

   • The duration of taking Reagila is determined by the doctor and depends on the nature and severity of the disease, as well as the patient's response to treatment.
   • Stopping Reagila should be done gradually under the supervision of a physician to prevent possible withdrawal symptoms.

Use Reagils during pregnancy

Use of cariprazine (Reagil) during pregnancy should be done with extreme caution as there is evidence of potential risks to the fetus. A study in mice has shown that cariprazine may interfere with cholesterol biosynthesis in the fetal brain, which increases levels of toxic oxysterols in the brain and may be associated with the occurrence of disorders similar to those seen in Smith-Lemli-Opitz syndrome, a rare genetic disorder that results in multiple developmental defects (Genaro-Mattos et al., 2020).

Given the possible risks, the use of cariprazine during pregnancy requires careful weighing of the potential benefits and risks to the health of the mother and child. Always consult your doctor to assess all possible risks and benefits before starting treatment with this drug during pregnancy.

Contraindications

1. Severe hepatic impairment: Cariprazine is metabolized in the liver, so its use in patients with severe hepatic impairment may result in increased blood concentrations of the drug and increased side effects.
2. Severe renal impairment: Similar to hepatic impairment, severe renal impairment may affect the excretion of the drug and its metabolites, requiring dosage adjustment or alternative treatment.
3. Interaction with CYP3A4 inhibitors: Cariprazine is metabolized by the CYP3A4 enzyme, and its concomitant administration with strong inhibitors of this enzyme may significantly increase the blood levels of cariprazine, increasing the risk of side effects.

Side effects Reagils

1. Drowsiness: Many people may feel sleepy or tired while taking Rexulti. This may affect their ability to perform daily tasks.
2. Dizziness: Some patients may experience dizziness or a feeling of unsteadiness when changing body position.
3. Tremor: This may manifest as slight shaking of the hands or other parts of the body.
4. Sleepy restless legs: Some people may experience discomfort in their legs while sleeping, causing them to move or become restless.
5. Increased appetite and weight gain: Some patients may experience increased appetite and weight gain while taking Rexulti.
6. Problems with concentration and memory: Some people may notice problems with concentration and memory while taking this drug.
7. Sexual Function Problems: Some patients may experience problems with libido, erection, or orgasm.
8. Increased Prolactin Levels: Rexulti may increase levels of the hormone prolactin, which can cause problems with hormonal balance and milk production in women and men.
9. Increased Blood Sugar and Lipids: Some patients may experience increased blood sugar and lipids.

Overdose

1. Increased unwanted side effects: This may include drowsiness, dizziness, insomnia, anxiety, agitation, muscle weakness, digestive problems (eg, nausea, vomiting, diarrhea), possible changes in blood pressure and heart rate.
2. Risk of serious side effects: There may be an increase in serious side effects such as akinesia, extrapyramidal symptoms (movement disorders), seizures, cardiovascular complications (eg, arrhythmias), and others.
3. Potentially Fatal Effects: In case of significant overdose, a potentially fatal condition may occur, especially if the cardiovascular and respiratory systems are impaired.

Interactions with other drugs

1. Centrally acting drugs: Cariprazine may enhance the sedative effects of other centrally acting drugs such as benzodiazepines, narcotic analgesics and hypnotics. This may increase the risk of drowsiness and central nervous system depression.
2. Antihistamines: Cariprazine may enhance the sedative effects of antihistamines.
3. Drugs affecting the cytochrome P450 system: Cariprazine is metabolized in the liver by cytochrome P450 enzymes, especially the CYP3A4 isoenzyme. Drugs that induce (eg, rifampicin, carbamazepine) or inhibit (eg, ketoconazole, clarithromycin) this system may alter blood levels of cariprazine.
4. Drugs that increase the QT interval: Cariprazine itself may increase the QT interval. Combination with other drugs that also increase the QT interval (eg, antiarrhythmic drugs, antidepressants) may increase the risk of cardiac arrhythmias.
5. Drugs that reduce gastric acidity: Drugs that reduce gastric acidity (eg, antacids, proton pump inhibitors) may reduce the absorption of cariprazine from the gastrointestinal tract and decrease its effectiveness.