Reagila

Reagila (cariprazine) is a medicine used to treat schizophrenia in adults and to treat bipolar disorder in adults and children 10 years of age 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 other medicine, Reagila may cause side effects, so it is important to take it under the supervision of a doctor and follow his or her recommendations.

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 symptoms of bipolar disorder, including mania (elevated mood, increased energy and activity, aggression) and depression (low mood, loss of interest in usual activities, drowsiness).

Release form

Reagila is usually available as tablets for oral administration.

Pharmacodynamics

1. Dopamine receptor antagonism: Reagila is an antagonist of dopamine D2 and D3 receptors. This means that it blocks the action of dopamine, a neurotransmitter associated with psychosis. Antagonism of dopamine receptors helps reduce 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. It may improve your mood and 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 psychiatric disorders is still being studied. Modulation of the glutamate system may improve cognitive function and help reduce negative symptoms of schizophrenia.
4. Minimal effects on other receptors: Reagila is generally well tolerated and is associated with fewer side effects due to antagonism of histamine, muscarinic and α1-adrenergic receptors.

Pharmacokinetics

1. Absorption: Reagila is usually well absorbed from the gastrointestinal tract after oral administration. Maximum plasma concentrations are usually achieved approximately 1-3 hours after administration.
2. Distribution: Reagila has a high degree of binding to plasma proteins (about 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 with the participation of cytochrome P450 enzymes, mainly with the participation of the CYP3A4 isoenzyme. The main 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 through the intestines.
5. Half-life: The half-life of Reagila is approximately 2-3 days after daily dosing.
6. Food: Food may increase the area under the plasma concentration curve (AUC) and the maximum concentration (Cmax), but this does not usually have a clinically significant effect on its effectiveness.
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, as well as the use of other drugs.
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. Method of application:

   • Reagil tablets are usually taken orally, regardless of meals.
   • The tablets should be swallowed whole, without chewing or splitting 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 Reagila administration is determined by the doctor and depends on the nature and severity of the disease, as well as the patient’s response to treatment.
   • Discontinuation of Reagila should be carried out gradually under the supervision of a physician to prevent the possible occurrence of withdrawal syndrome.

Use Reagils during pregnancy

The use of cariprazine (Reagil) during pregnancy should be carried out with extreme caution, as there is evidence of potential risks to the fetus. A study in mice showed 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 disorders similar to those seen in Smith-Lemli-Opitz syndrome, a rare genetic disorder causing to numerous 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 threats to the health of the mother and child. Always consult your health care professional to evaluate the 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 drug concentrations in the blood 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 dose adjustment or alternative treatment.
3. Interaction with CYP3A4 inhibitors: Cariprazine is metabolized by the CYP3A4 enzyme, and concomitant use with strong inhibitors of this enzyme may significantly increase cariprazine blood levels, increasing the risk of side effects.

Side effects Reagils

1. Drowsiness: Many people may feel drowsy 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 feel 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 difficulty concentrating 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 flow in women and men.
9. Elevated blood sugar and lipid levels: Some patients may experience increased blood sugar and lipid levels.

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: Potentially increased serious side effects such as akinesia, extrapyramidal symptoms (motor disturbances), seizures, cardiovascular complications (eg, arrhythmias), and others.
3. Potentially fatal consequences: In case of significant overdose, a potentially fatal condition can occur, especially if the functions of the cardiovascular and respiratory systems are impaired.

Interactions with other drugs

1. Central-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 effect of antihistamines.
3. Drugs affecting the cytochrome P450 system: Cariprazine is metabolized in the liver with the participation of cytochrome P450 enzymes, especially the CYP3A4 isoenzyme. Drugs that induce (eg, rifampicin, carbamazepine) or inhibit (eg, ketoconazole, clarithromycin) this system may alter cariprazine blood levels.
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 stomach acid: Drugs that reduce stomach acid (eg, antacids, proton pump inhibitors) may reduce the absorption of cariprazine from the gastrointestinal tract and reduce its effectiveness.