Parnasan, tablets 10 mg, 30 pcs.

Parnasan is an antipsychotic (neuroleptic). Antipsychotic action is caused by blockade of dopamine D2-receptors of mesolimbic and mesocortical system; sedative action – by blockade of adrenoreceptors of reticular formation of brain stem; antiemetic action – by blockade of dopamine D2-receptors of trigger zone of vomiting center; hypothermic action – by blockade of dopamine receptors of hypothalamus. It also acts on m-choline, H1-histamine and some subclasses of serotonin receptors. Eliminates productive symptomatology of psychosis (delirium, hallucinations); reduces hostility, suspiciousness, emotional and social autism. Rarely causes extrapyramidal disorders.

Pharmacokinetics

Absorption of olanzapine is high, not dependent on ingestion; Tmax after oral administration is 5-8 h. When administered in the dose range 1-20 mg, plasma concentrations change linearly, proportional to the dose. At plasma concentrations of 7-1000 ng/ml, the binding to proteins is 93%; mainly to albumin and alpha1-acid glycoprotein. Penetrates through histohaematic barriers, including the BBB. It is metabolized in the liver by conjugation and oxidation, no active metabolites are formed, the main pharmacological activity of the drug is due to olanzapine. The main circulating metabolite is glucuronide, which does not penetrate the BBB. CYP1A2 and CYP2D6 cytochrome P450 isoenzymes are involved in the formation of N-desmethyl and 2-hydroxymethyl metabolites of olanzapine. Smoking, sex, and age affect T1/2 and plasma clearance. Non-smokers (clearance 18.6 l/h, T1/2 38.6 h), smokers (clearance 27.7 l/h, T1/2 30.4 h), women (clearance 18.9 l/h, T1/2 36.7 h), men (clearance 27.3 l/h, T1/2 32.3 h). In patients older than 65 years, T1/2 is 51.8 h and plasma clearance is 17.5 l/h; in patients younger than 65 years, T1/2 is 33.8 h and plasma clearance is 18.2 l/h. Plasma clearance is lower in patients with hepatic impairment, women and non-smoking patients compared to the respective patient groups. It is excreted mainly by the kidneys (60%) as metabolites.

Indications

Active ingredient

Composition

1 tablet contains:
active ingredient: 10 mg,
excipients:
core: crospovidone; MCC (type 102); MCC (type 200); ludipress (lactose monohydrate 93%, povidone 3.5%, crospovidone 3.5%); magnesium stearate;
film coating: Opadry II white (polyvinyl alcohol – 45.52%, titanium dioxide – 32%, talc – 20%, soy lecithin – 2%, xanthan gum – 0.48%)

How to take, the dosage

Overly, regardless of meals, with water.

In schizophrenia: In adults, the recommended initial dose is 10 mg/day.

In an episode of mania associated with bipolar disorders: in adults, 15 mg/day as monotherapy or 10 mg/day in combination with lithium or valproic acid (maintenance therapy at the same dose).

Prevention of mania recurrence in bipolar disorder: The recommended starting dose of the drug in remission is 10 mg/day. For patients already treated with Parnasan® for a mania episode, maintenance therapy is given at the same dose. During therapy with Parnasan® in case of a new manic, mixed or depressive episode, the drug dose should be increased with additional treatment of mood disorders, if necessary, in accordance with clinical indications.

The daily dose of the drug in the therapy of schizophrenia, manic episode, or for the prevention of recurrence of bipolar disorder may be 5-20 mg/day, depending on the clinical condition of the patient. Increasing the dose beyond the recommended initial dose is possible only after an adequate reassessment of the patient’s clinical condition and is usually done at intervals of at least 24 hours.

Patients in Special Populations

Elderly patients: Decreasing the starting dose (to 5 mg/day) is not usually recommended, but may be possible in patients older than 65 years if there are risk factors.

Patients with hepatic and/or renal disease: reduction of the initial dose to 5 mg/day is recommended. In moderate hepatic impairment (cirrhosis, class A or B according to Child-Pugh scale) the initial dose is 5 mg/day, further dose increase with caution is possible.

Women: no dosing adjustment is required compared to men.

Non-smoking patients: No dose adjustment is required compared to smoking patients.

If a patient has more than one factor that may affect absorption (female sex, older age, nonsmokers), the initial dose of the drug may need to be reduced. If necessary, the dose may be further increased with caution.

Special Instructions

There are very rare reports of the development of hyperglycemia and/or decompensation of diabetes mellitus, sometimes accompanied by the development of ketoacidosis or diabetic coma, including reports of several fatal cases. A causal relationship between antipsychotics and these conditions has not been established. In some cases, there has been a prior increase in body weight, which may have been a predisposing factor. Patients with diabetes mellitus or risk factors for this disease are recommended to have regular clinical monitoring and control of blood glucose concentrations.

In case of changes in lipid concentrations, correction of therapy is required.

If Parnasan® is stopped abruptly, very rarely (less than 0.01%) the following symptoms may occur: sweating, insomnia, tremor, anxiety, nausea, or vomiting.

A gradual reduction of the dose is recommended when withdrawing the drug.

Anticholinergic activity. Since clinical experience with Parnasan® in patients with comorbidities is limited, the drug should be used with caution in patients with benign prostatic hyperplasia, paralytic ileus, closed-angle glaucoma.

Parnasan® has been used in patients with Parkinson’s disease psychosis induced by dopamine mimetics. Parnasan® is not recommended for therapy of Parkinson’s disease psychoses induced by dopamine mimetics. Parkinsonian symptoms and hallucinations are aggravated. However, the drug Parnasan® did not outperform placebo in the treatment of psychosis.

The treatment of psychosis and/or behavioral disorders in dementia. Parnasan® is not indicated due to increased mortality and increased risk of cerebrovascular events (stroke, transient ischemic attacks) in this patient population. These patients had prior risk factors (history of cerebrovascular events, transient ischemic attack, arterial hypertension, smoking) and comorbidities and/or medication use that were temporally associated with cerebrovascular events. The increase in mortality is independent of the dose of Parnasan® or the duration of therapy. Risk factors predisposing to increased mortality include: age over 65 years, dysphagia, sedation, malnutrition and dehydration, lung diseases (e.g., pneumonia, including aspiration), concomitant use of benzodiazepines. However, increased mortality in the Parnasan® groups compared with placebo was independent of these risk factors.

In therapy with antipsychotics, improvement in a patient’s clinical condition occurs over a period of several days to several weeks. During this time, the patient needs close monitoring.

Liver function impairment. At the beginning of therapy, asymptomatic increase of liver transaminases activity (ALT and ACT) is possible. Caution should be exercised when using Parnasan® in patients with initially elevated ACT and/or ALT activity, hepatic insufficiency and conditions, potentially limiting liver function, as well as in patients taking hepatotoxic drugs. In case of ALT and/or ACT increase during the drug therapy it is recommended to monitor the patient and, possibly, decrease the drug dose. If hepatitis (including hepatocellular, cholestatic or mixed) is diagnosed, Parnasan® should be discontinued.

Hematological disorders. The drug should be used with caution in patients with leukopenia and/or neutropenia of any genesis, myelosuppression of drug genesis, as well as during radiation or chemotherapy, due to concomitant diseases, in patients with hypereosinophilic states or myeloproliferative diseases. Neutropenia has often been observed when concomitant administration of Parnasan® and valproic acid (see “Adverse effects”).

Malignant neuroleptic syndrome (MNS). MNS is a potentially life-threatening condition associated with therapy with antipsychotic agents (neuroleptics), including Parnasan®.

The clinical manifestations of MNS: fever, muscle rigidity, disturbance of consciousness, vegetative disorders (unstable pulse or labile BP, tachycardia, increased sweating, arrhythmia). Additional symptoms of MNS: increased CPK activity, myoglobinuria (against the background of rhabdomyolysis) and acute renal failure. All neuroleptics, including Parnasan®, should be discontinued in case of development of symptoms of WNS and also increase of body temperature without evident reasons.

Convulsive syndrome. Parnasan® should be used with caution in patients with a history of seizures or in patients with factors decreasing seizure threshold. Convulsions have rarely been registered against the background of Parnasan® administration.

Late dyskinesia. Therapy with Parnasan® was associated with significantly lower incidence of tardive dyskinesia compared to haloperidol. The risk of tardive dyskinesia increases with increasing duration of therapy. If signs of this condition appear in a patient taking Parnasan®, the drug should be withdrawn or the dose should be reduced. Symptoms of tardive dyskinesia may increase or manifest after drug withdrawal.

General activity with respect to the CNS. Caution should be exercised with concomitant use of other centrally acting drugs and alcohol.

Cerebrovascular adverse events, including stroke in elderly patients with dementia. Postural arterial hypotension is uncommon in elderly patients. In patients over 65 years of age, periodic BP monitoring is recommended. Parnasan® should be used with caution in patients with established prolonged QTc interval, especially in elderly patients, with congenital syndrome of prolonged QT interval, chronic heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia.

In administration of Parnasan® very rarely (less than 0.01%) cases of venous thromboembolism have been reported. A cause-effect relationship between Parnasan® therapy and venous thromboembolism has not been established. Because patients with schizophrenia often have acquired risk factors for venous thrombosis, all other possible other factors (e.g., immobilization) should be identified and preventive measures taken.

In vitro, olanzapine is antagonistic to dopamine and, like other neuroleptics, can theoretically inhibit levodopa and dopamine agonists.

The effect on the ability to drive and operate machinery. Since Parnasan® may cause drowsiness and dizziness, patients should be cautious while operating machinery requiring high concentration, including driving motor transport.

Contraindications

With caution: renal failure; hepatic failure; benign prostatic hyperplasia; closed-angle glaucoma; paralytic intestinal obstruction; epilepsy; seizure syndrome in anamnesis; leukopenia and/or neutropenia of various genesis; myelosuppression of various genesis, including.ч. myeloproliferative diseases; hypereosinophilic syndrome; cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension; congenital increase in the QT interval on ECG (increase in the corrected QT interval – QTc – on ECG) or in the presence of conditions that can potentially cause QT interval prolongation (such as simultaneous use of QT interval prolongers); chronic heart failure; hypokalemia; hypomagnesemia); elderly age; as well as concomitant use of drugs of central action; phenylketonuria; immobilization; pregnancy.

Side effects

Nervous system disorders: very frequently – somnolence; frequently – dizziness, akathisia, parkinsonism, asthenia, dyskinesia; rarely – convulsive syndrome (more often in the background of convulsive syndrome in anamnesis); very rarely – malignant neuroleptic syndrome – MNS (see “Special indications”), dystonia (including oculogyric crisis) and tardive dyskinesia. Symptoms such as increased sweating, insomnia, tremor, anxiety, nausea, or vomiting have very rarely been noted with abrupt withdrawal of Parnasan®.

Particular systemic diseases: frequently – arterial hypotension (including orthostatic); infrequently – bradycardia with or without collapse; very rarely – prolongation of QTc interval in ECG (see “Special indications”). “

Particular indications>, ventricular tachycardia/fibrillation and sudden death (see “Particular indications”), thromboembolism (including pulmonary embolism and deep vein thrombosis).

Digestive system disorders: often – transient anticholinergic effects, including constipation and dry mouth; transient, asymptomatic increase of liver transaminases activity (ALT, ACT, especially at the beginning of therapy – see “Indications. “Special indications”); rarely – hepatitis (including hepatocellular, cholestatic or mixed liver damage); very rarely – pancreatitis.

Mechanical system disorders: very common – weight gain; common – appetite increase, hypertriglyceridemia; very rare – hyperglycemia and/or diabetes decompensation, sometimes manifested by ketoacidosis or coma, including lethal outcome; hypercholesterolemia, hypothermia.

Hematopoietic organs: often – eosinophilia; rarely – leukopenia; very rarely – thrombocytopenia, neutropenia.

Musculoskeletal system: very rare – rhabdomyolysis.

Urogenital system disorders: very rare – urinary retention, priapism.

The skin: rare – skin rash; infrequent – photosensitization reactions; very rare – alopecia.

Allergic reactions: rare – skin rash; very rare – anaphylactoid reactions, angioedema, pruritus or urticaria.

Others: frequent – asthenia, peripheral edema; very rare – withdrawal syndrome.

Laboratory findings: very common – hyperprolactinemia; but clinical manifestations (e.g., gynecomastia, galactorrhea, and enlarged mammary glands) are rare. Most patients had spontaneous normalization of prolactin levels without therapy withdrawal. Rarely – transient, asymptomatic increase of ALT, ACT activity; infrequent – increase of KFC activity; very rare – increase of ALT and total bilirubin activity; in single cases – increase of plasma glucose over 200 mg/dl (suspected diabetes mellitus), 160-200 mg/dl (suspected hyperglycemia) in patients with baseline glucose concentration less than 140 mg/dl. Increases in triglycerides (20 mg/dL from baseline), cholesterol (0.4 mg/dL from baseline), and asymptomatic eosinophilia (isolated cases) were observed.

In elderly patients with dementia, a higher incidence of death and cerebrovascular disorders (stroke, transient ischemic attacks) has been reported in studies. Gait disturbances and falls were very frequent in this category of patients. Pneumonia, elevated body temperature, lethargy, erythema, visual hallucinations, and urinary incontinence were also common.

Worsening of Parkinsonian symptoms and the development of hallucinations were frequently reported among patients with drug-induced (on dopamine agonists) psychoses in the background of Parkinson’s disease.

There are data about development of neutropenia (4.1%) during combined therapy with valproic acid in patients with bipolar mania. Concomitant therapy with valproic acid or lithium contributes to an increased incidence (more than 10%) of tremor, dry mouth, increased appetite or increased body weight. Speech disorders (1 to 10%) have also been reported.

Pregnancy use

Due to limited experience with the drug in pregnant women, Parnasan® should be used in pregnancy only if the expected benefits justify the potential risk to the fetus. Women should be informed about the necessity of informing the physician about an occurred or planned pregnancy during therapy with Parnasan®. There have been isolated reports of tremor, arterial hypertension, lethargy and somnolence in children born to mothers who took olanzapine in the third trimester of pregnancy. Parnasan® has been shown to penetrate into breast milk in studies. The average dose (mg/kg) received by the infant at maternal Css was 1.8% of the maternal dose of Parnasan® (mg/kg). Breastfeeding during therapy is not recommended.

Similarities