Pharmacological action Abilify 5 mg
Antipsychotic (neuroleptic). It is assumed that the therapeutic effect of aripiprazole in schizophrenia due to a combination of partial agonist activity on dopamine D2-and serotonin 5HT1a receptors and antagonist activity at serotonin 5HT2-receptors.
Aripiprazole has a high affinity in vitro for dopamine D2-D3-and receptors, serotonin 5HT1a-and 5HT2a-receptors and moderate affinity for dopamine D4-, serotonin 5HT2c-and 5HT7-, α1-adrenoceptors and histamine H1-receptors. Aripiprazole is also characterized by a moderate affinity for serotonin reuptake sites and the lack of affinity for muscarinic receptors. In experimental animal studies, aripiprazole showed antagonism against dopaminergic hyperactivity and dopaminergic agonism on hypoactivity. Some of the clinical effects of aripiprazole may be explained by interaction with dopamine and serotonin receptors.
Pharmacokinetics Abilify 5 mg
Absorption
After oral aripiprazole is rapidly absorbed from the gastrointestinal tract. Cmax in the plasma is achieved in 3-5 h. The absolute bioavailability – 87%. Eating does not affect the bioavailability of aripiprazole.
Distribution and metabolism
Css is reached after 14 days. Drug accumulation after repeated admission to predict. Indicators of the pharmacokinetics of aripiprazole at steady state are proportional to dose. There was no diurnal variation of distribution of aripiprazole and its metabolite degidroaripiprazola.
Aripiprazole extensively distributed in tissues, Vd is 4.9 L / kg. At therapeutic concentrations greater than 99% of aripiprazole bound to serum proteins, primarily albumin.
It is established that degidroaripiprazol, the major metabolite in human plasma, has the same affinity for the D2-receptor dopaminvym as aripiprazole.
Aripiprazole undergoes first-pass metabolism only minimally. Metabolized in the liver in three ways: dehydrogenation, hydroxylation, and N-dealkylation. In vitro hydroxylation and dehydrogenation occurs under the action of aripiprazole isozymes CYP3A4 and CYP2D6, N-dealkylation – CYP3A4.
Active Abilifaya mainly due to the presence of unchanged aripiprazole.
In equilibrium, the AUC degidroaripiprazola in plasma is about 39% of the AUC of aripiprazole.
Breeding
The average T1 / 2 of aripiprazole – about 75 hours
After a single dose of 14C-labeled aripiprazole, approximately 27% and 60% of the radioactivity is determined in urine and feces, respectively. Less than 1% of unchanged aripiprazole determined in urine and about 18% of the dose in unchanged form excreted in the feces. The total clearance of aripiprazole is 0.7 ml / min / kg, mainly due to elimination of the liver.
Aripiprazole does not affect the pharmacokinetics and pharmacodynamics of warfarin, ie does not displace warfarin from binding to blood proteins.
Statement Abilify 5 mg
- Treatment of acute schizophrenia, maintenance treatment of schizophrenia;
- Treatment of acute manic episodes of bipolar disorder type I and for maintenance therapy in patients with bipolar I disorder, manic or recently had a mixed episode.
Dosage and administration Abilify 5 mg
In schizophrenia are encouraged to nominate Abilify the initial dose of 10-15 mg 1 time / day, regardless of the meal. The maintenance dose is 15 mg / day. In clinical studies, the effectiveness of the drug in doses ranging from 10 to 30 mg / day.
In the manic episodes of bipolar disorder Abilify should be a time / day of eating, starting with a dose of 15 or 30 mg / day. Change the dose, if necessary, should be conducted at intervals of not less than 24 h. In clinical studies demonstrated the efficacy of the drug in doses of 15-30 mg / day for manic episodes when administered for 3-12 weeks. Safety of the drug in doses of 30 mg / day in clinical trials has not been evaluated.
When monitoring patients with bipolar I disorder and manic or mixed episodes who had no symptoms while taking Abilify for 6 weeks at a dose of 15 mg / day or 30 mg / day at an initial dose of 30 mg / day, set a favorable effect a maintenance therapy. You should periodically examine patients to determine whether to continue maintenance therapy.
Patients with renal insufficiency, hepatic insufficiency (classes A, B and C Child-Pugh) do not require a change in dose.
Although the experience with the drug in patients over the age of 65 years is limited, dose adjustment for these patients is required.
Side effect Abilify 5 mg
Determining the frequency of side effects: Very common – ≥ 10%, and often – by ≥ 1% to
Cardio-vascular system: often – orthostatic hypotension, tachycardia, rarely – bradycardia, palpitation, myocardial infarction, lengthening the interval QT, heart failure, hemorrhage, atrial fibrillation, heart failure, AV-block, myocardial ischemia, deep vein thrombosis, phlebitis , beats, rare – vasovagal syndrome, enlargement of the heart, atrial flutter, thrombophlebitis, intracranial hemorrhage, cerebral ischemia is very rare – fainting.
Part of the digestive system: very often – nausea, loss of appetite, and often – dyspepsia, vomiting, constipation, rarely – increased appetite, gastroenteritis, difficulty swallowing, flatulence, gastritis, dental caries, gingivitis, hemorrhoids, gastroesophageal reflux, gastrointestinal bleeding, periodontal abscess, swelling of the tongue, fecal incontinence, colitis, rectal hemorrhage, stomatitis, mouth ulceration, cholecystitis, fekaloma, candidiasis of the oral mucosa, gallstone disease, eructation, gastric ulcer, rarely – esophagitis, bleeding gums, inflammation of the tongue, bloody vomiting, intestinal bleeding, duodenal ulcer, cheilitis, hepatitis, enlarged liver, pancreatitis, perforation of the bowel is very rare – increased ALT, AST, alkaline phosphatase.
From the Musculoskeletal System: Frequent – myalgia, muscle cramps, rare – pain in joints and bones, myasthenia gravis, arthritis, arthritis, muscle weakness, cramps, bursitis, very rarely – increased activity of CPK, rhabdomyolysis, tendenit, tenobursit, rheumatoid arthritis, myopathy.
From the central and peripheral nervous system: very often – insomnia, somnolence, akathisia, and often – dizziness, tremor, extrapyramidal syndrome, psychomotor agitation, depression, nervousness, excessive salivation, hostility, suicidal thoughts, manic thoughts, staggering, confusion, resistance to the implementation of passive movements (cogwheel sign), rarely – dystonia, muscle spasms, weakening of concentration, paresthesia, tremor of limbs, impotence, bradykinesia, decreased / increased libido, panic reaction, apathy, dyskinesia, memory loss, stupor, amnesia, stroke hyperactivity, depersonalization, dyskinesia, a syndrome of “restless legs” (akathisia), myoclonus, depressed mood, increased reflexes, slowing of mental function, increased sensitivity to irritants, hypotension, impaired oculomotor reactions, rarely – delirium, euphoria, bukkoglossalny syndrome, akinesia, depression of consciousness until he lost consciousness, decreased reflexes, obsessive thoughts, CSN.
The respiratory system: often – shortness of breath, pneumonia, rarely – asthma, epistaxis, hiccup, laryngitis, rarely – hemoptysis, aspiration pneumonia, increased sputum, dryness of the nasal mucosa, pulmonary edema, pulmonary embolism, hypoxia, respiratory distress, apnea .
From the senses: common – conjunctivitis, ear pain, rarely – dry eyes, eye pain, tinnitus, otitis media, cataracts, loss of taste, blepharitis, rarely – increased tearing, blinking, otitis externa, amblyopia, deafness, diplopia, eye hemorrhage, photophobia.
Urogenital system: frequent – incontinence, infrequent – cystitis, frequent urination, Leucorrhoea, urinary retention, hematuria, dysuria, renal failure, albuminuria, kidney stones, nocturia, polyuria, urination, amenorrhea, premature ejaculation, vaginal bleeding , vaginal candidiasis, uterine bleeding, menorrhagia, rarely – burning in the urethra, glycosuria, painful erection, pain in the breast, cervicitis, galactorrhea, anorgasmia, gynecomastia (breast enlargement in men).
From a metabolism: common – weight loss, increased CPK, rarely – dehydration, edema, hypercholesterolemia, hyperglycemia, hypokalemia, diabetes mellitus, hyperlipidemia, hypoglycemia, thirst, increased blood urea, hyponatremia, iron deficiency anemia, elevated creatinine, bilirubinemia, elevated lactate dehydrogenase levels, obesity, rare – hyperkalemia, gout, hypernatremia, cyanosis, acidification of urine, hypoglycemic reaction.
Dermatologic reactions: often – dry skin, itching, sweating, skin ulcer, rarely – acne, vezikulobuleznaya (bubble), rash, eczema, alopecia, psoriasis, seborrhea, rarely – Makulo-papular rash, exfoliative dermatitis.
By the immune system: very rare – allergic reactions (anaphylaxis, angioedema, pruritus and urticaria).
Part of the body as a whole: often – flu-like syndrome, peripheral edema, chest pain, neck, rarely – pelvic pain, face edema, malaise, photosensitivity, jaw pain, fever, stiff jaw, bloating, pressure in the chest; rarely – sore throat, stiffness in the back, heavy-headedness, candidiasis, stiffness in the throat, Mendelson’s syndrome, heat stroke.
Contraindications Abilify 5 mg
- Age 18 years;
- Hypersensitivity to aripiprazole and other ingredients.
Used with caution in patients with cardiovascular diseases (coronary heart disease or with prior myocardial infarction, heart failure and conduction disorders), cerebrovascular diseases and conditions predisposing to hypotension (dehydration, hypovolemia, and antihypertensive drugs) in connection with the possibility of orthostatic hypotension in patients with seizures or suffer from diseases that are possible convulsions in patients with an increased risk of hyperthermia (eg, intense physical exercise, overheating, taking anticholinergic drugs, dehydration due to the ability of neuroleptics interfere with thermoregulation) in patients with increased risk of aspiration pneumonia because of the risk of esophageal motor function disorders and aspiration, in patients suffering from obesity and diabetes in the presence of family history.
Pregnancy and breast feeding Abilify 5 mg
Adequate and well controlled clinical studies on the safety of pregnancy was conducted. Aripirazol can be used during pregnancy when the potential benefits of therapy to the mother outweighs the potential risk to the fetus.
It is not known whether aripirazol released in breast milk in humans. We do not recommend the use of aripiprazole during the period of lactation (breastfeeding).
Experimental studies have shown that aripiprazole is excreted in the milk of lactating rats.
Application of human liver Abilify 5 mg
Patients with hepatic insufficiency (classes A, B and C Child-Pugh) do not require a change in dose.
Use in renal impairment Abilify 5 mg
Patients with renal insufficiency not require a change in dose.
Cautions Abilify 5 mg
The tendency to suicidal thoughts and attempts is characteristic of psychosis, so during the medical therapy requires careful medical supervision.
The risk of developing tardive dyskinesia increases with duration of neuroleptic therapy, so the appearance of aripiprazole on symptoms of tardive dyskinesia should reduce the dose or stop medication. After discontinuation of these symptoms may temporarily worsen or even appear for the first time.
In the treatment of antipsychotic drugs, including aripiprazole may develop NMS, which is manifested hyperpyrexia, muscle rigidity, mental disorders and the autonomic nervous system instability (irregular pulse and blood pressure, tachycardia, sweating, arrhythmia). In addition, sometimes there are increased activity of CK, myoglobinuria (rhabdomyolysis) and acute renal failure. In the case of NMS symptoms or unexplained fever all antipsychotics, including aripiprazole should be abolished.
Hyperglycemia, in some cases severe and associated with ketoacidosis, which can lead to hyperosmolar coma and even death, was observed in patients treated with atypical antipsychotics. Although the association between atypical antipsychotics and impaired hyperglycemic type remains unclear, patients diagnosed with diabetes should regularly determine the level of glucose in the blood while taking atypical antipsychotics. Patients who present risk factors for diabetes (obesity, diabetes, family history), while taking atypical antipsychotics should be the determination of glucose in the blood at the beginning of the course and periodically during drug administration. In all patients treated with atypical antipsychotics require continuous monitoring for symptoms of hyperglycemia (strong thirst, frequent urination, polyphagia and weakness).
Effects on ability to drive and control mechanisms
As with other antipsychotic drugs, the appointment Abilifaya patient should be warned about the dangers of working with moving machinery and driving.
Overdose Abilify 5 mg
In clinical studies described cases of accidental or intentional overdose with aripiprazole, a single dose to 1080 mg, accompanied by death. Symptoms include nausea, vomiting, fatigue, diarrhea and drowsiness. In hospitalized patients, found no clinically significant changes in vital signs, laboratory parameters and ECG.
Post-marketing experience a single dose of adult patients up to 450 mg of aripiprazole suggests the possible development of arrhythmias. In addition, the described cases of overdose of aripiprazole in children (reception up to 195 mg). Potentially dangerous overdose symptoms include extrapyramidal disorders and transient loss of consciousness.
Treatment: supportive care, ensuring an adequate airway, oxygenation, ventilation and effective symptomatic treatment. It should be drug reactions. Should be started immediately monitoring the performance of the heart to the registration of ECG to detect arrhythmias. After a confirmed or suspected overdose of aripiprazole should be close medical supervision until the disappearance of all symptoms.
Activated charcoal (50 g) injected one hour after administration of aripiprazole, decreased the AUC and Cmax of aripiprazole by 51% and 41% respectively, which allows us to recommend its use in overdose.
Although reliable data on the use of hemodialysis in an overdose of aripiprazole no beneficial effect of this method is unlikely, because Aripiprazole is not excreted by the kidneys in unchanged form and is largely bound to plasma proteins.
Drug Interactions Abilify 5 mg
There were no significant effect of histamine blocker famotidine H2-receptor, which causes a strong inhibition of secretion of hydrochloric acid in the stomach, on the pharmacokinetics of aripiprazole.
There are various ways of metabolism of aripiprazole, including involving enzymes CYP2D6 and CYP3A4. In studies in healthy potent inhibitors of CYP2D6 (quinidine) and CYP3A4 (ketoconazole) reduced the clearance of aripiprazole when administered at 52% and 38% respectively (while the use of inhibitors of CYP3A4 and CYP2D6 should reduce the dose of aripiprazole).
Receiving Aripiprazole 30 mg simultaneously with carbamazepine, a potent inducer of CYP3A4, was accompanied by a decrease in Cmax and AUC of aripiprazole by 68% and 73%, respectively, and a decrease in Cmax and AUC of its active metabolite degidroaripiprazola 69% and 71% respectively. We can expect similar effects and other powerful inducers of CYP3A4 and CYP2D6.
In the metabolism of aripiprazole in vitro do not participate enzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP2E1, and therefore unlikely to interact with drugs and other factors (eg smoking) that can inhibit or activate these enzymes.
Simultaneous treatment with lithium or valproate with aripiprazole 30 mg 1 time / day had no clinically significant effect on the pharmacokinetics of aripiprazole.
In clinical studies of aripiprazole at doses of 10-30 mg / day had no significant effect on the metabolism of substrates of CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin) and CYP3A4 (dextromethorphan). In addition, aripiprazole and its major metabolite degidroaripiprazol not change the metabolism of the enzyme CYP1A2 in vitro. It is unlikely a clinically significant effect of aripiprazole on drugs metabolised by these enzymes with.
