Ridona

Therapeutic indications

Ridona is indicated in the treatment of patients with schizophrenia, including the first episode of psychosis, schizophrenic exacerbations, chronic schizophrenia and other psychotic conditions that present positive signs such as: hallucinations, delusions, delusions, altered thinking, hostility and / or negative symptoms. , for example: affective flattening, emotional and social abandonment, decreased expression, poverty in language.

In the treatment of schizophrenia, Ridona can also relieve affective symptoms (depression, guilt). It is also indicated as therapy for the prevention of relapses (acute exacerbations) in patients with chronic schizophrenia. In addition, Ridona is indicated for the treatment of conduct disorders in patients with dementia who present with symptoms such as aggressiveness (verbal outbursts, physical violence), activity disorders (agitation, wandering), or prominent psychotic symptoms.

Pharmacological action

Ridone contains Risperidone, an atypical antipsychotic belonging to a new chemical class, the benzisoxazole derivatives, a selective monoaminergic antagonist with high affinity for the serotoninergic 5HT2 and dopaminergic D2 receptors. It also binds to alpha1 adrenergic receptors and, with lower affinity, alpha2 adrenergic receptors and H1 histaminergic receptors. It has no affinity for cholinergic receptors.

The potent D2 antagonism of Risperidone causes improvement of the positive symptoms of schizophrenia. The affinity for D1 receptors that causes motor depression and induces catalepsy is lower with Risperidone than with classic neuroleptics. The balance in the dopaminergic and serotoninergic antagonism allows to extend the therapeutic activity on the negative and affective symptoms and, in addition, to reduce the appearance of extrapyramidal symptoms.

Pharmacokinetics

Risperidone is completely absorbed after oral administration and reaches its maximum plasma concentrations in 1 or 2 hours. Meals do not affect its absorption.

The relative bioavailability of the Ridona coated tablet is 94% compared to the solution.

The absolute oral bioavailability of Risperidone is 70% and that of the active phase (Risperidone and 9-hydroxy-risperidone) reaches 100%. Risperidone is partially metabolized in the liver and its 9-hydroxy-risperidone metabolite is equally active.

The half-life of Risperidone is approximately 3 hours; the elimination half-life of the active fraction (Risperidone and 9-hydroxy-risperidone) is 24 hours.

Stable concentrations of Risperidone are reached in one day in most patients, while those of the active fraction are achieved within 5 or 6 days and within the doses used therapeutically, the concentrations are proportional to the doses.

Risperidone is rapidly distributed and the binding with plasma proteins is 90% for Risperidone and 77% for the active metabolite.

In patients with normal kidney function, approximately 70% of the dose is excreted in the urine and 15% in the faeces. Renal clearance decreases in elderly patients and in those with moderate or severe renal compromise, requiring dose adjustments. In patients with hepatic impairment, the free fraction of Risperidone in plasma is increased by around 35% due to a decrease in the concentration of albumin and alpha1 acid glycoprotein, which is why the dose should be reduced.


Contraindications

Known hypersensitivity to Risperidone or some of its components.

Warnings

Rare cases have been reported of neuroleptic malignant syndrome characterized by hypertemia, muscle stiffness, altered consciousness and evidence of instability, associated with elevated CPK, possible to complicate myoglobinuria and renal compromise and also associated with the use of other antipsychotic drugs. In these cases, the use of Risperidone should be discontinued. As with any antipsychotic drug, the occurrence of extrapyramidal symptoms appears to be a risk factor for the development of tardive dyskinesia. If symptoms or signs of tardive dyskinesia appear, discontinuation of treatment should be considered. In some patients, Risperidone and its metabolite may increase the QT interval of the ECG; This is also possible with higher doses than recommended, or concomitantly using other drugs that lengthen the QT interval.

Caution

Due to its alpha-blocking activity, orthostatic hypotension may occur, especially during the dose titration period. Therefore, it should be used with caution in patients with proven heart disease.

It should also be used with caution in patients with Parkinson’s disease, since, theoretically, it can cause deterioration of the disease.

Risperidone may induce a dose-dependent increase in plasma prolactin concentration and consequently galactorrhea, gynecomastia, menstrual cycle disturbances, or amenorrhea. This fact is a factor of potential importance if the administration of Risperidone is required to patients with detected breast cancer.

Because neuroleptics lower the seizure threshold, they should be used with caution in patients with epilepsy. As with other antipsychotics, patients should be warned of the possibility of weight gain.

Elderly patients and patients with renal and hepatic impairment require dose adjustments and subsequent increases. Like other neuroleptics, Risperidone can interfere with activities that require mental alertness; therefore, patients should be advised to drive or operate machinery.

Pregnancy and reproduction

The safety of Risperidone during pregnancy has not been definitively established and although no teratogenic effects have been verified in experimental animal studies, Risperidone can only be used during pregnancy when the benefits outweigh the risks derived from its use.

Lactation

Experimental animal studies revealed that Risperidone is excreted in milk. Although this fact is not known in humans, patients should not breastfeed while receiving Risperidone.

Employment in pediatrics

Its administration is not recommended for children under 15 years of age.

Drug interactions

Ridone should be used with caution in combination with other centrally acting drugs.

It can antagonize the effects of levodopa and other dopamine agonists.

Carbamazepine and other liver enzyme-inducing drugs lower the plasma levels of the active antipsychotic portion of Risperidone, requiring dose adjustments.

Phenothiazines, tricyclic antidepressants, and some beta-blockers may increase the plasma concentrations of Risperidone but not its fractions.

The protein binding of Risperidone is not modified by other concomitant medications, regardless of their respective protein binding.

Abuse and dependency

Risperidone has not been fully studied regarding its possibility of causing abuse, tolerance and dependence. The studies carried out showed no tendency for search behaviors. These facts do not allow predicting its abusive potential. It is necessary to investigate in patients the antecedents of abuse, signs of misuse or abuse of Risperidone such as an increase in the dose, development of tolerance or presence of search behaviors.

Composition

Ridona 1

 

Each coated tablet contains:

Risperidone     1mg

C.S. excipients

Ridona 2

 

Each coated tablet contains:

Risperidone     2mg

C.S. excipients

Ridona 3

 

Each coated tablet contains:

Risperidone     3mg

C.S. excipients

Ridona 4

 

Each coated tablet contains:

Risperidone     4mg

C.S. excipients

Ridona Solution

Each ml of solution contains:

Risperidone     1mg

C.S. excipients


Administration route

Oral


Posology and method of administration

Adults: Ridona can be administered in 1 or 2 daily doses. The 6 mg daily dose should be titrated in 3 days. In both acute and chronic patients, treatment should start with 2 mg of Ridona per day, increasing them to 4 mg per day on the second day and 16 mg per day on the third day.

Thereafter, the dose can be adjusted as needed, and it is recommended to do so at intervals of not less than 1 week, increasing or decreasing the dose by 2 mg per day. In general, the effective dose range varies between 4 mg and 16 mg per day. The usual dose is generally observed in the range of 4 mg to 8 mg per day, although some respond appropriately to lower doses. Doses greater than 10 mg of Risperidone per day have not generally been shown to provide greater benefits, and may instead increase the risk of extrapyramidalism. Doses greater than 10 mg daily should be used only when the expected benefit outweighs the risk. In the absence of extensive experience, doses greater than 16 mg per day should not be used.

Elderly: It is recommended to use 2 doses daily, starting with 1 mg of Ridona per day and adjust it by 1 mg per day, until reaching 2-4 mg daily. Perform dose increases at intervals of not less than 1 week.

Children: There is no experience in children under 15 years of age.

Kidney and liver disease: The doses and mode of administration are similar to those indicated for the elderly.

Replacement of other antipsychotics: When it is necessary to replace other antipsychotics, it is advisable to gradually discontinue previous treatment, while starting Ridone therapy. When a depot injectable antipsychotic is to be replaced, Ridone treatment should be started instead of the next scheduled injection. Periodically reevaluate the need to use antiparkinson medication.

Procedure for correct administration of the oral solution:

      1. Insert the dosing syringe into the plunger pressing all the way down into the bottle.
      2. Aspirate the indicated dosage by rotating the plunger, taking into account that the liquid contained in the syringe exactly matches the level indicated by the doctor.
      3. Administer the preparation by mixing it with a little water or orange juice.

Storage Recommendations

Do not leave medicines within the reach of children.

Store in a cool place below 30 °C.


Presentation

Ridona Coated Tablets: Box containing three blisters with 10 coated tablets each.

Ridona Oral Solution: Box containing a bottle with 30 ml of solution with a glass and a dosing syringe.

Side effects

Ridona is generally well tolerated. The most common adverse effects associated with discontinuation of treatment and possible or probably related to the drug are extrapyramidal symptoms, such as vertigo, hyperkinesia, drowsiness and nausea.

Although the incidence and severity of extrapyramidal symptoms are rare, in some cases tremor, rigidity, sialorrhea, bradykinesia, akathisia, and acute dystonia can occur. These symptoms are generally mild and reversible after dose reduction and / or administration of antiparkinsonian medication.

Rarely, cases of neuroleptic malignant syndrome characterized by hyperthermia, muscle stiffness, autonomic instability, altered consciousness, and elevated CPK have been reported. In these cases, like all antipsychotic drugs, it should be discontinued.

As with other classical neuroleptics, isolated cases of water intoxication with polydipsia hyponatremia or syndrome of inappropriate antidiuretic hormone secretion have been reported in schizophrenic patients. Other reported adverse effects are listed below:

Psychiatric. Common: drowsiness, decreased libido, nervousness. Occasional: decreased concentration, depression, apathy, catatonic reaction, euphoria, increased libido, amnesia. Rare: emotional lability, nightmares, delirium, abandonment syndrome, yawning.

Central and peripheral nervous system. Frequent: increased sleep duration. Occasional: dysarthria, vertigo, stupor, paraesthesia, confusion. Rare: aphasia, cholinergic syndrome, hypoesthesia, lingual paralysis, leg cramps, torticollis, hypotonia, coma, migraine, hyporeflexia, choreoathetosis.

Gastrointestinal. Common: anorexia, decreased salivation. Occasional: flatulence, diarrhea, increased appetite, stomatitis, melena, dysphagia, hemorrhoids, gastritis. Rare: fecal incontinence, belching, gastroesophageal reflux, gastroenteritis, esophagitis, discoloration of the tongue, tongue edema, cholelithiasis, diverticulitis, gingivitis, discoloration of stool, gastrointestinal bleeding, hematemesis.

General. Common: fatigue. Occasional: edema, stiffness, discomfort, flu-like symptoms. Rare: paleness, enlarged abdomen, ascites, allergic reactions, sarcoidosis, redness.

Respiratory. Occasional: hyperventilation, bronchospasm, pneumonia, stridor. Rare: asthma, increased sputum, aspiration.

Skin and annexes. Common: hyperpigmentation, photosensitivity. Occasional: increased or decreased sweating, acne, alopecia, hyperkeratosis, itching, exfoliation of the skin. Rare: bulla, skin ulcers, worsening of psoriasis, furunculosis, warts, lichenoid dermatitis, hypertrichosis, genital itching, urticaria.

Cardiovascular. Occasional: palpitations, hypertension, hypotension, AV block, myocardial infarction. Rare: ventricular tachycardia, angina, atrial extrasystoles, T wave inversion, ST segment depression, ventricular extrasystoles, myocarditis.

Visuals. Occasional: disorders of accommodation, xerophthalmia. Rare: diplopia, eye pain, blepharitis, photopsia, photophobia, abnormal tearing.

Metabolic and nutritional. Occasional: hyponatremia, weight increase or decrease, CPK increase, thirst, diabetes mellitus. Rare: decreased serum iron, cachexia, dehydration, hypokalemia, hypoproteinemia, hyperphosphatemia, hypertriglyceridemia, hyperuricemia, hypoglycemia.

Urinals. Common: polyuria / polydipsia. Occasional: urinary incontinence, hematuria, dysuria. Rare: urinary retention, cystitis, kidney failure.

Musculoskeletal. Occasional: myalgia. Rare: osteoarthritis, synostosis, bursitis, arthritis, skeletal pain.

Female reproductive system. Common: menorrhagia, orgasmic dysfunction, vaginal dryness. Occasional: non-puerperal lactation, amenorrhea, mastalgia, leucorrhea, mastitis, dysmenorrhea, perineal pain, breakthrough bleeding, vaginal bleeding.

Male reproductive system. Common: erection disorders. Occasional: disorders of ejaculation.

Hepatobiliary. Occasional: increased TGO and TGP. Rare: liver failure, cholestatic hepatitis, cholelithiasis, hepatitis, hepatocellular damage.

Coagulation disorders. Occasional: epistaxis, purple. Rare: hemorrhage, superficial phlebitis, thrombophlebitis, thrombocytopenia.

Auditory and vestibular. Rare: tinnitus, hyperacusis, decreased hearing.

Hematological. Occasional: anemia, hypochromic anemia. Rare: normocytic anemia, leukocytosis, leukopenia, lymphadenopathy, Peuger-Huet abnormality.

Endocrine. Rare: gynecomastia, mastalgia in males, antidiuretic hormone disorders.

Sensory. Rare: bitter taste.

«This medicine must be used exclusively under prescription and medical supervision and cannot be repeated without a new prescription».