Akatinol Memantine, 90 pcs., 10 mg, film-coated tablets

5 mg tablet 10 mg tablet 7-14-21-28 mg cap,sprinkle,ER 24hr dose pack 2 mg/mL solution

Trade names in Russia

Akatinol Memantine, Noodzheron, Maruxa, Memantinol, Memantal, Memantine, Memantine Canon, Memaneurin, Memantine-Richter, Memantine hydrochloride, Memikar, Alzeim, Memantine-TL

Release form

• Tablets: 10 mg, 20 mg
• Oral drops 10 mg/ml
• Oral dispersible tablets: 10 mg, 20 mg

Indications

◊ Recommendations of the Russian Ministry of Health

F00.0 Dementia in early onset Alzheimer's disease

F00.1 Late-onset dementia in Alzheimer's disease

F00.2 Dementia in Alzheimer's disease, atypical or mixed type

F00.9 Dementia in Alzheimer's disease, unspecified

◊ FDA recommendations

G.30 Alzheimer's disease

◊ EMA recommendations

G.30 Alzheimer's disease

◊ Using Off-label

• Vascular dementia
• Dementia with Lewy bodies
• Frontotemporal dementia
• HIV-associated dementia
• Multiple sclerosis

Mechanism of action and pharmacokinetics

Memantine acts as a non-competitive antagonist of NMDA receptors, preferentially binding to cation channels gated by NMDA receptors. Long-term increases in glutamate levels in the brains of patients with dementia counteract the voltage-gated block of NMDA receptors by Mg2+ ions and promote a continuous influx of Ca2+ ions into cells, which ultimately leads to neuronal degeneration. Studies show that memantine binds to NMDA receptors more effectively than Mg2+ ions, and thereby effectively blocks the long-term influx of Ca2+ ions through the NMDA channel, maintaining transient physiological activation of the channels with higher concentrations of glutamate released into the synapses. Thus, memantine protects against chronically elevated glutamate concentrations. Memantine also exhibits serotonin (5-HT3) receptor antagonistic activity with potential similar to that of the NMDA receptor, and reduced nicotinic acetylcholine receptor antagonistic activity. This drug does not bind to γ-aminobutyric acid (GABA), benzodiazepine, dopamine, adrenergic, histamine, glycine, or voltage-gated calcium, sodium, or potassium receptors.

• Little metabolized;
• It is excreted almost unchanged in the urine;
• The half-life is approximately 60-100 hours; peak plasma concentrations after 3-7 hours [3].
• Minimal inhibition of CYP450 enzymes.

Experience of many years of using Akatinol for Alzheimer's disease

The progressive dementia seen in Alzheimer's disease has long been considered fatal because it is associated with the death of brain cells and subsequent brain atrophy. The last decade has forced us to reconsider these seemingly unshakable provisions (1). In the group of new ones, the so-called. Akatinol was identified as an “antidementia” drug. The results of its successful clinical trial in our country were published back in 1995 (2). Subsequently, it turned out that this drug is effective not only for mild, but also for moderately severe and severe types of dementia. It turned out that with its use, even at the stage of severe dementia, it is possible to compensate for neurodegenerative destruction due to the activation of glumatergic neurons and synapses with preserved NMDA receptors that have not yet died, but are in a state of apoptosis (functional shutdown, programmed cell death).

However, to achieve a therapeutic result, therapy with Akatinol must be long-term (at least six months) and continuous (3). To date, Akatinol has become one of the popular means of medical practice in the treatment of dementia. But as the scope of its use expands, questions arise regarding the limits of the duration of treatment with this drug (limited to certain courses or for life), regimens and dosages of maintenance therapy, and its tolerability by older people when taken for many years. Traditional clinical trials cannot answer these questions. There are no special studies yet on the effectiveness of extremely long-term (many years) and maintenance therapy for dementia. In these conditions, you have to turn to medical experience.

Quite early (since 1996) we began treating patients with dementia due to Alzheimer's disease and other brain pathologies (usually vascular) with Akatinol. Akatinol is very popular in psychiatric institutions in the Moscow region. Experience of its long-term use is gradually accumulating.

In this regard, the case of treatment of severe dementia as a result of Alzheimer's disease, which we have been observing since the summer of 1999 (for 11 years), is noteworthy. This case is especially interesting in that continuous and long-term use of Akatinol for 5-6 months of therapy led to a “dramatic” exit from typical Alzheimer’s type dementia to a state of practical recovery. This case was presented at the “Man and Medicine” congress in Moscow in 2000 (4).

Let us remember that we were talking about a woman born in 1924 (she is now 86 years old), who has been observed at the regional psychoneurological clinic since April 1999. Here is a brief history of her illness.

Anamnesis.

Ill since 1997 (since 74 years old). The disease developed gradually and progressed slowly. Its first manifestation was difficulties in writing. I first noticed this when I received my pension from the savings bank, when I suddenly couldn’t reproduce my signature, although I had done it easily before. Now her painting turned out different every time, and it was necessary to repeat it many times. Then her husband noticed that she stopped reading books and solving crossword puzzles, although she had previously been very keen on these activities. Then I lost interest in watching TV. Physical weakness began to gradually increase. There was uncertainty when walking, coordination of movements was impaired to such an extent that at times she had to be supported so that she did not fall. She actually fell several times, then got up on her own. She didn’t show any concern about this. Irritability appeared, which was not typical for her before. Memory noticeably weakened. She began to speak little and quietly. Sometimes my husband had the feeling that she was no longer understanding him: he asked her about one thing, and in response she said something unrelated to the question. All this grew slowly over two years, from the end of 1997 to 1999. Neither the patient nor her husband paid serious attention to these disorders, since they considered them manifestations of age.

In January 1999 (at the age of 75) she began to complain of pain in the heart area, palpitations, interruptions in heart function intensified once again, shortness of breath and swelling of the lower extremities appeared. I contacted a therapist at the district clinic. The ECG revealed atrial fibrillation. A diagnosis was made: “ischemic arrhythmia”. Treatment was carried out on an outpatient basis (finoptin, veroshpiron, furosemide, aspirin). The somatic condition returned to normal relatively quickly. However, after this, his mental state began to deteriorate. It started with difficulties in orientation in space, which intensified. I began to get confused even in my own apartment. Gradually I completely lost my bearings: I couldn’t find my bed or toilet. Memory has deteriorated sharply. I even began to forget my husband’s name. Then she stopped recognizing her own granddaughter and asked who she was; I didn’t recognize my husband either. Sometimes she took him for her father, but more often she considered him just a stranger. She began to claim that she lives in Dnepropetrovsk, where she actually lived many years ago. She began to speak very little, quietly, in short, monosyllabic phrases. At times she became aggressive and complained that they wanted to rob her. She claimed that some women and men were entering the apartment and allegedly beating her. In this state, on the advice of a neurologist, in April 1999 she first turned to a psychiatrist at the regional psychoneurological clinic (her husband took her there). Mental status (according to the outpatient card): “Moves with difficulty, with the help of her husband. Contact is difficult. With difficulty, only after repeating it twice, she understands the questions addressed to her. Emotionally depressed. Lethargic, apathetic. Intellectually and mnestically, the ability to write is sharply reduced. According to the husband, he occasionally experiences auditory hallucinations, especially at night, and expresses ideas of persecution.”

During an examination at home in April 1999: “He has no sense of time. He cannot name not only the current day or month, but also the current year and even the season of the year. Looking out the window, he says that it is winter now. Cannot give his passport details, age, year of birth. Doesn't recognize her husband. He believes that he is with his relatives, but he does not know where. He doesn’t know his way around the apartment, doesn’t know how to get to the toilet or to his room. It is difficult to attract attention. The facial expression is unclear, the look is confused. Accounting operations are difficult. Unable to perform sequential subtraction. Tries to read, but cannot reproduce what he read. He takes dictation, but what is written can be understood with difficulty. He misses letters in a letter, distorts the style of letters, superimposes the spelling of some letters onto others, and does not complete some words. Of the several objects shown to her, she could name only two (a watch and a pen). He reacts to his inadequacy with a helpless smile. Elementary praxis (the ability to dress, wash, eat) is still preserved.”

In May 1999, a computed tomography scan of the brain was performed. A symmetrical proportional expansion of the lateral ventricles, cisterns, Sylvian fissures, the third ventricle, and, to a lesser extent, the convexity grooves of both cerebral hemispheres was revealed. Periventricular symmetrical zones of low density without mass effect. The midline structures are not displaced. The fourth ventricle is not dilated. The skull bones are not deformed. Conclusion: “Atrophic hydrocephalus of mixed type is above average, with a predominance of internal; signs of an intracranial space-occupying process were not identified. After the examination, the patient was diagnosed with dementia due to Alzheimer’s disease, and disability group I was established.”

The patient began taking Akatinol in mid-April 1999 according to the standard regimen. At first there was no change in her condition. The disease continued to progress: she lost her remaining self-care skills and could not dress or wash herself. However, subsequently (after about a month of therapy) further deterioration stopped. Then the first signs of improvement appeared in the form of general calmness, a decrease in nighttime agitation and getting ready for the trip. After 5 months of continuous use of the drug (August 1999), the husband was surprised to notice that the patient began to independently find her way to the toilet and generally began to navigate better in the apartment. Then she suddenly became interested in TV, began watching TV shows, at first everything in a row, then she began to look for a TV program and choose what to watch. At the end of September, she suddenly sat down in the kitchen and, as she loved before, began to play solitaire. By the beginning of 2000, my memory and orientation were almost completely restored, and I had a desire to communicate with old friends by phone. All subsequent time, the patient’s condition and behavior did not differ from what it was before the illness. In the spring of 2000, she underwent successful cataract surgery, after which she began to read a lot again. She spent the summer at the dacha, often remained there alone, without her husband, and dealt with all household chores on her own. She continued to take Akatinol at a daily dose of 30 mg (15 mg 2 times a day). In March 2001, due to interruptions in the supply of the drug, the daily dose was reduced to 10 mg, and soon she felt the onset of absent-mindedness, difficulty concentrating, and weakening of memory. I increased the dose to 20 mg per day, after which all the emerging disorders disappeared.

In April 2001, the patient underwent a control clinical study. The somatic condition is satisfactory, there were no signs of coronary heart disease or vascular damage to the brain, and she did not contact a therapist or neurologist. Mental status: “Accurately oriented in time.” Understands where she is and who surrounds her, the purpose of the examination and conversation with her, willingly and with interest participates in the conversation, gives complete and adequate answers to questions. The mood is even. Names the objects presented to her correctly. Sequential subtraction by 7 is quick and error-free. Accurately follows all instructions during the examination. Reading and writing are not impaired. She understands that she suffered some kind of severe mental disorder, but she cannot talk about its manifestations in herself, since it does not remain in her memory. He remembers nothing about meetings with the doctor, about the examinations performed, or about his behavior at home during that period. She knows about what happened to her only from the words of her husband. I am happy that I got rid of this serious illness and live a full, satisfying life. During an experimental psychological study, it was noted that the patient correctly understands the purpose of the study, demonstrates sufficient productivity of mental performance, an average rate of sensorimotor reactions according to the Schulte table, but is easily tired. Her self-esteem is unstable, and on the “happiness” scale she is sharply overestimated (“at my age I am the happiest”). Intellectual-mnestic activity reveals a slight decrease in intellectual capabilities, slowness and difficulty of intellectual processes and counting operations. The learning curve for 10 words is sufficient (7, 8, 8, 9, 8, 8), after an hour (delayed reproduction) - 6 words. When ten words are reproduced, extra words appear, which may indicate slight depletion of the mnestic function. Semantic memorization (mediation according to Leontiev, IV series) is available: out of 9 mediated words, he accurately names 7, approximately - 1, does not remember - 1. Computed tomography was repeated - in the same institution and on the same apparatus as the first tomographic study in May 1999. Conclusion: “In a series of control axial tomograms in comparison with X-ray CT data from May 18, 1999, the CT picture is without significant dynamics. Manifestations of high-grade mixed atrophic hydrocephalus persist.”

For the next 5 years, the patient led an active lifestyle. For the first two or three years, she spent the summer at the dacha, often remained there alone and successfully coped with all the chores around the house and caring for the plants. Then, by the age of 82, she gradually moved away from the dacha worries, which had become unbearable for her. Living in a city apartment, she led a normal, familiar lifestyle - she watched TV shows, read a lot, talked with friends and family. There were practically no complaints about my health; I didn’t go to the clinic. In 2004, she gradually reduced the dose of Akatinol to 10 mg per day. During this period, she experienced the sudden death of her husband, who earlier, when she was in a state of dementia, provided constant care for her and provided her with early, and most importantly, continuous and long-term use of Akatinol. She took her husband’s death hard, but without any health consequences. The medicine (Akatinol) continued to be taken at the same dose (10 mg per day). At first, the city health department allowed the patient to be provided with the drug at the expense of municipal funds, but then this was denied to her. Financial difficulties arose. Her family helped her regularly buy the drug, but for reasons of economy, she began to try to take breaks in treatment or reduce the dose. It turned out that already a week after the break in taking the drug, her condition worsened: difficulties appeared in understanding her surroundings, which was especially noticeable when trying to fill out receipts for utility bills (she could not calculate how much to pay for light). In her head, as she herself later said, “some kind of mess” arose. These phenomena disappeared soon after resuming Akatinol intake or increasing its dose. So, empirically, experimentally, she herself determined that the lower limit of the daily daily dose of Akatinol for her is 5 mg (half a tablet). As soon as she switched to taking ¼ tablet (2.5 mg), problems with comprehension, memory and counting immediately appeared. I still regularly take ½ tablet daily. (5 mg) Akatinol. The condition remains normal for her. Lives with his grandson, who very often goes on business trips for several days. She runs the household independently, prepares food for him and for herself. Copes with all these tasks without problems. She willingly agreed to go to the clinic for a follow-up examination. On the way, she discovered excellent navigation skills - in the intricate labyrinths of blocks of standard five-story buildings, where the young driver got confused, she, like a “navigator,” led him to the right road.

Clinical and psychological research was carried out at the Clinic of Nervous Diseases named after. AND I. Kozhevnikov (I.M. Sechenov Medical Academy) in February 2006. The examination was conducted by Doctor of Medical Sciences V.V. Zakharov. Here are his results: “When examined in clear consciousness, contact, adequate, correctly oriented in place and time. Moderate cognitive impairment was noted (MMSE 25 points). Neuropsychological testing reveals moderate impairment of executive functions in the form of decreased speech fluency and decreased concentration. Memory is impaired to a small extent, mainly of the dynamic type. Speech, praxis, gnosis - without visible disturbances. The neurological status shows revival of oral automatism reflexes, hypomimia, and hypokinesia. There are no paresis. Tendon reflexes are lively, uniform, and there are no pathological ones. Sensitivity is intact. Coordinator tests are performed satisfactorily. She is stable in the Romberg position. Gait is without any peculiarities. Controls the pelvic organs. An MRI examination of the head was performed. The resulting images revealed that the midline structures of the brain were not displaced. The lateral ventricles are symmetrically dilated. The subarachnoid spaces of the cerebral hemispheres are expanded in the temporoparietal regions. The cerebrospinal junction is without visible changes, the lower edge of the cerebellar tonsils is located at the level of Chamberlain's line. The structure of the spinal cord parenchyma at the level of C1-3 vertebrae is homogeneous. No additional formations were identified in the spinal canal at the upper cervical level. To this day (May 2010) she is alive and active, although physically weakened. Recently I called and introduced myself: “This is the exhibit that you showed to the doctors.” I inquired about the possibilities of obtaining Akatinol at preferential rates. She still takes it at her established maintenance dose (5 mg per day). There are no intellectual problems."

This incident turned out to be instructive for us in many ways. In addition to the fact that the amazing effectiveness of Akatinol in fairly severe dementia was obvious, we could see that the elimination of symptoms of dementia is not associated with the restoration of dead brain tissue: the pattern of atrophy of the cerebral cortex and subcortical structures remained stable during therapy. But the process of neurodestruction was stopped, atrophic phenomena no longer increased. Hence the obvious conclusion: the neuroprotective effect is associated with the functional restoration of neurons, with their removal from the state of apoptosis. We believe that a certain role in this was played by the fact that treatment was started relatively early, two months after the onset of the clinical picture of dementia itself.

It became clear that dementia therapy could not be stopped. Akatinol, with all its wonderful medicinal properties, is not an etiotropic drug in the treatment of Alzheimer's disease, but rather a pathogenetic drug. While normalizing one of the important links in the pathogenesis of the disease, it does not eliminate the disease itself and therefore must be used for life.

It turned out to be very important that long-term therapy with Akatinol for Alzheimer’s disease can be carried out according to the model of maintenance therapy for chronic diseases, and to maintain the therapeutic effect, the doses of the drug with which treatment began are not needed at all - but not below a certain minimum. For this patient, the ratio of therapeutic (20 mg) and maintenance (5 mg) doses was 1:4. Perhaps this rule is of a general nature and can be applied to other patients - this should be confirmed by further experience. But the very fact that the therapeutic and maintenance doses are not equal is very important, since this circumstance significantly reduces the cost of treatment. In modern conditions, this purely economic factor is often a decisive condition for success.

Other observations in which we were also able to see a very significant reverse trend in the symptoms of dementia taught us how important it is to maintain continuity of therapy in severe dementia. Thus, in one of the hospitals in the Moscow region, a patient was discharged in good condition, with restoration of her intellectual status, and she was recommended to continue treatment at home. But the patient’s husband thought that she was already good, there was no money to purchase a sufficiently expensive drug, and she was left without treatment. Two months later she was again admitted to hospital with severe dementia. Repeated therapy with Akatinol was unsuccessful - obviously, the resource for functional restoration of brain activity in Alzheimer's disease is very small and must be protected.

As for moderate and especially mild forms of dementia, here, according to our observations, intermittent therapy is also possible - for example, 2-3 month courses with a break of 3-4 weeks. However, experience shows that rigid regimens in the treatment of Alzheimer's disease are inappropriate. Everything here is individual, and that is why it is so important to establish an atmosphere of therapeutic cooperation with the patient (and his family). The patient, as was shown in the above case, is himself able to notice the beginning of intellectual deterioration (“mess in the head”) and understand that this is a signal for the immediate resumption of therapy.

Long-term therapy with Akatinol is safe; we encountered virtually no undesirable effects during its implementation.

Treatment regimen

◊ Dosage and dose selection

• 10 mg twice daily
• 28 mg once daily (long-acting)
• Initially 5 mg/day, increase by 5 mg every week; a dose greater than 5 mg should be divided into parts; the maximum dose is 10 mg twice a day [1].
• Long-acting: initially 7 mg once daily, can be increased by 7 mg weekly, maximum dose 28 mg once daily [1].

◊ How quickly it works

Memory improvement is not expected, and it will take months for the condition to stabilize [1].

◊ Expected result

Slows down the development of the disease, but does not stop the degenerative process.

◊ If it doesn't work

• Change the dose, switch to a cholinesterase inhibitor (galantamine, donepezil, rivastigmine) or add a cholinesterase inhibitor.
• Reconsider the diagnosis to rule out depression or non-Alzheimer's dementia [1].

◊ How to stop taking it

• There were no cases of withdrawal syndrome.
• Theoretically, discontinuation of dosage may cause memory impairment and changes in behavior that may remain uncorrected after resumption or initiation of dosage [1].

◊ Treatment combinations

• Atypical antipsychotics for behavior correction;
• Antidepressants for depression, apathy, loss of interest;
• Can be combined with cholinesterase inhibitors;
• Carbamazepine, oxcarbamazepine for behavioral disorders;

Akatinol Memantine, 90 pcs., 10 mg, film-coated tablets

INSTRUCTIONS for medical use of the drug Akatinol Memantine

I APPROVED

Head of the Department of State Control of Medicines and Medical Equipment of the Ministry of Health of the Russian Federation

Approved by the Pharmacological Committee of the Ministry of Health of Russia

Chemical name:

1-amino−3,5-dimethyl-adamantane hydrochloride 3,5-dimethyl-tricyclo-(3,3,1,137)-decane−1-aminohydrochloride

Description

Film-coated tablets, cream-colored, oblong, biconvex, scored on each side. Covered with a film shell. Tablet length 12.6±0.1 mm; width 5.6±0.1 mm; height 3.7±0.1 mm.

Drops are a colorless transparent solution.

Compound

1 film-coated tablet contains: active substance - memantine hydrochloride 10 mg, excipients: lactose 174.75 mg, MCC 52.100 mg, colloidal silicon dioxide 1.25 mg, talc 11.15 mg, magnesium stearate 0.75 mg; film coating: methacrylic acid copolymer 1.446 mg, sodium lauryl sulfate 0.010 mg, polysorbate 80 0.034 mg, triacetin 0.150 mg, SE 0.01 mg, talc 0.35 mg.

1 ml of drops contains: active substance - memantine hydrochloride 10 mg, excipients: potassium sorbate 2 g, sorbitol solution 100 ml, purified water 888 ml.

Pharmacological properties

Pharmacodynamics

Memantine has a modulating effect on the glutamatergic system, being a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors. It has a pathogenetic effect on degenerative processes in the central and peripheral nervous system. Regulates ion transport - blocks calcium channels. Has a neuroprotective effect. Normalizes membrane potential. Improves the process of nerve impulse transmission. Improves cognitive processes, memory and learning ability, increases daily activity.

Pharmacokinetics

After oral administration, Akatinol Memantine is quickly and completely absorbed. Cmax in blood plasma is achieved within 2–6 hours. With normal renal function, no accumulation of the drug was observed. Elimination occurs in two phases. T1/2 is, on average, in the first phase - 4-9 hours, in the second - 40-65 hours. It is excreted mainly by the kidneys (75-90%).

Indications

Degenerative dementia (Alzheimer's type), vascular dementia, mixed dementia of all degrees of severity. Weakening of memory, ability to concentrate, ability to learn. Cerebral and spinal spastic syndrome due to traumatic brain injury, multiple sclerosis, stroke.

Contraindications

— Individual hypersensitivity to the drug.

— Severe renal dysfunction.

- Pregnancy.

- Breast-feeding.

Prescribe with caution to patients with thyretoxicosis and epilepsy.

Side effects

Dizziness, feeling tired, anxiety, increased excitability, nausea.

Interaction

With simultaneous use of Akatinol Memantine with barbiturates, neuroleptics, and anticholinergics, the effect of the latter may be enhanced. When used together, Akatinol Memantine may change the effect of dantrolene or baclofen, so the doses of the drugs should be selected individually.

Overdose

The manifestations of the described side effects may increase.

Directions for use and doses

The dosage regimen is set individually. It is recommended to begin treatment with the administration of minimally effective doses.

Adults with dementia syndrome are prescribed a dose of 5 mg/day during the 1st week of therapy, and a dose of 10 mg/day during the 2nd week. During the 3rd week - at a dose of 15–20 mg/day. If necessary, it is possible to further increase the dose weekly by 10 mg until a daily dose of 30 mg is reached. For movement disorders caused by pathology of the central nervous system, a daily dose of 10 mg is prescribed during the 1st week of treatment, a dose of up to 10 mg/day during the 2nd week, and 20–30 mg during the 3rd week. . If necessary, it is possible to further increase the dose by 10 mg weekly until a daily dose of 60 mg is reached.

The approximate maintenance dose is 10–20 mg/day.

The daily dose is evenly divided into several doses throughout the day, the drug should be taken with meals, the last dose is recommended to be taken before dinner.

For patients with impaired renal function, the dosage regimen is set individually, depending on clinical effectiveness, under the control of renal function during treatment.

Children are prescribed a dose of 500 mcg/kg/day.

special instructions

For elderly patients, it is preferable to prescribe the drug in the form of drops. The optimal dose is achieved gradually, with the dose increasing every week.

Release form

Film-coated tablets: packs of 30 and 90 pcs.

Drops for oral administration: in bottles of 50 and 100 ml.

Storage conditions

List B.

Store at a temperature not exceeding 25°C out of the reach of children.

Best before date

Tablets - 3 years, drops - 5 years.

Conditions for dispensing from pharmacies

On prescription.

Enterprise - 60318, Germany, Frankfurt am Main

Special patient groups

◊ Patients with kidney problems

• No special dose selection is required.
• In severe renal failure, reduce the dose.

◊ Patients with liver disease

No special dose selection is required.

◊ Patients with heart disease

No special dose selection is required.

◊ Elderly patients

The same pharmacokinetics as in young patients.

◊ Children and teenagers

The use of memantine has not been studied.

◊ Pregnant women

• Risk Category B – animal studies have not shown any risk of adverse effects on the fetus, and there have been no adequate studies in pregnant women;
• Not recommended for pregnant women or those preparing to conceive [1].

◊ Breastfeeding

Memantine is not known to pass into breast milk, but all psychotropic drugs pass into breast milk. It is recommended that you stop taking memantine or stop breastfeeding [1].

Akatinol Memantine

Treatment should be initiated and supervised by a physician experienced in diagnosing and treating Alzheimer's dementia.

Therapy should only be started with a caregiver who will regularly monitor the patient's medication intake.

Diagnosis of the disease should be carried out in accordance with current recommendations.

The tolerability and dosage of memantine should be reviewed on a regular basis, preferably within three months of starting treatment. Thereafter, the clinical benefit of memantine and the patient's tolerance to treatment should be reassessed on a regular basis in accordance with current clinical guidelines.

Maintenance treatment can be continued indefinitely as long as the therapeutic effect is favorable and as long as the patient tolerates memantine treatment.

If there is no evidence of therapeutic efficacy or if the patient is intolerant to treatment, discontinuation of memantine should be considered.

The drug should be taken orally once a day at the same time, regardless of meals.

The maximum daily dose is 20 mg.

To reduce the risk of adverse reactions, increase the initial dose to a maintenance dose by titrating 5 mg per week over the first 3 weeks as follows:

1st week (days 1-7): prescribed 5 mg per day.

Week 2 (days 8-14): 10 mg per day is prescribed.

Week 3 (days 15-21): 15 mg per day is prescribed.

4th week and beyond: prescribed 20 mg per day.

The recommended maintenance dose is 20 mg per day.

Tablets with other dosages are available for titration with increasing doses.

Elderly patients

According to clinical studies, the recommended dose for patients over 65 years of age is 20 mg per day.

Kidney failure

In patients with mild renal impairment (creatinine clearance 50-80 ml/min), no dose adjustment is required.

In patients with moderate renal failure (creatinine clearance 30-49 ml/min), the daily dose is 10 mg. If the drug is well tolerated for at least 7 days of treatment, the dose can be increased to 20 mg/day according to the standard titration scheme.

In patients with severe renal failure (creatinine clearance 5-29 ml/min), the daily dose is 10 mg.

Liver failure

In patients with mild or moderate hepatic impairment (Child-Pugh class A and B), no dose adjustment is required.

There are no data on the use of memantine in patients with severe hepatic impairment. Not recommended for use in patients with severe liver failure.

Side effects and other risks

◊ Mechanism of side effects

Presumably due to excessive effects on NMDA receptors.

◊ Side effects

• Dizziness, headache;
• Constipation;
• Dangerous side effects: seizures;
• Weight gain: no;
• Sedation: no, but weakness may occur [1].

◊ What to do about side effects

Wait; Reduce the dose, switch to another drug.

◊ Long-term use

After 6 months, treatment may no longer slow the progression of Alzheimer's disease [1].

◊Addiction

No.

◊ Overdose

• There were no deaths.
• Anxiety, psychosis, visual hallucinations, drowsiness, stupor, loss of consciousness.

Akatinol Memantine (tab.p.pl/vol.20mg No. 98)

A country

Germany
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.

Active substance

Memantine

Compound

1 film-coated tablet contains Active substance: memantine hydrochloride 20 mg Excipients: Microcrystalline cellulose: 263.5 mg Croscarmellose sodium: 13.5 mg Colloidal silicon dioxide: 1.5 mg Magnesium stearate: 1.5 mg Coating: Opadry pink: 12 mg consisting of: - Hypromellose: 7.5 mg - Titanium dioxide E171: 3.3984 mg - Macrogol 400: 0.75 mg - Red iron oxide E172: 0.2004 mg - Yellow iron oxide E172: 0.1512 mg Description Pink to light brown, oval-shaped tablets engraved with “20” on one side and “MEM” on the other side and film-coated. Release form: Film-coated tablets, 20 mg. 14 tablets with a dosage of 20 mg in a blister made of polyvinyl chloride film and aluminum foil. 2, 4 or 7 blisters along with instructions for use are placed in a cardboard box.

Pharmacological properties

Pharmacodynamics: Adamantane derivative. Being a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, it reduces the excessive stimulatory effect of cortical glutamate neurons on the neostriatum. Regulates ion transport, blocks calcium channels, normalizes membrane potential, improves the process of nerve impulse transmission. Improves cognitive processes, increases daily activity. Pharmacokinetics: After oral administration, it is quickly and completely absorbed. The maximum concentration in blood plasma is achieved within 2-6 hours. With normal renal function, no accumulation of the drug was observed. Excretion occurs in two phases. The half-life is 4-9 hours in the first phase, 40-65 hours in the second phase. About 80% of memantine is excreted unchanged. Metabolites do not have their own pharmacological activity. Excreted in urine. When urine is alkaline, excretion slows down.

Indications for use

Moderate to severe dementia in Alzheimer's disease.

Contraindications

Individual hypersensitivity to the drug, severe renal failure (creatinine clearance 5-29 ml/min), severe liver failure, pregnancy, breastfeeding, children under 18 years of age (due to insufficient data). With caution Prescribe with caution to patients with thyrotoxicosis, epilepsy, convulsions (including a history), simultaneous use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan), the presence of factors that increase urine pH (sudden change of diet, for example, switching to vegetarianism, heavy intake alkaline gastric buffers), severe urinary tract infections, myocardial infarction (history), heart failure functional class III-IV (NYHA classification), uncontrolled arterial hypertension, renal failure, liver failure.

Mode of application

The drug should be taken orally once a day and always at the same time, regardless of meals. Prescribed during the 1st week of therapy (days 1-7) at a dose of 5 mg/day, during the 2nd week (days 8-14) at a dose of 10 mg/day, during the 3rd week (days 15 -21) - at a dose of 15 mg/day, during the 4th week (days 22-28) - at a dose of 20 mg/day. The maximum daily dose is 20 mg. In patients over 65 years of age, as well as patients with a creatinine clearance of 50-80 ml/min, no dose adjustment is required. For patients with moderate renal failure (creatinine clearance 30-49 ml/min), the daily dose is 10 mg. Subsequently, if the drug is well tolerated for 7 weeks, the dose can be increased to 20 mg according to the standard regimen.

Side effect

Adverse reactions are classified according to clinical manifestations (according to damage to certain organ systems) and frequency of occurrence: very often (≥ 1/10), often (≥ 1/100 to From the body as a whole - general adverse reactions Often Headache Rarely Fatigue Infections Rarely Fungal infections Mental disorders Often Drowsiness Rarely Confusion Rarely Hallucinations* Frequency not established Psychotic reactions Cardiovascular system disorders Rare Increased blood pressure Rarely Venous thrombosis/thromboembolism Gastrointestinal disorders Common Constipation Rarely Nausea, vomiting Frequency not established Pancreatitis Disorders from the central and peripheral nervous system Often Dizziness Rarely Gait disturbance Very rarely Seizures *Hallucinations have been observed mainly in patients with Alzheimer's disease at the stage of severe dementia.There are isolated reports of the occurrence of these adverse reactions when using the drug in clinical practice (data obtained after the drug went on sale): Dizziness, drowsiness, increased excitability, increased fatigue, anxiety, increased intracranial pressure, nausea, hallucinations, headache, impaired consciousness, muscle hypertonicity, gait disturbances, depression, convulsions, psychotic reactions, suicidal thoughts, constipation , nausea, pancreatitis, candidiasis, increased blood pressure, vomiting, cystitis, increased libido, venous thrombosis, thromboembolism, allergic reactions.

Overdose

Symptoms: dizziness, tremor, agitation, drowsiness, confusion, agitation, stupor, convulsions, psychosis, aggressiveness, hallucinations, unsteadiness of gait, vomiting, diarrhea. Treatment: gastric lavage, taking activated carbon, symptomatic therapy. There is no specific antidote.

Interaction

When used simultaneously with levodopa drugs, dopamine receptor antagonists, and m-anticholinergic blockers, the effect of the latter may be enhanced. When used simultaneously with barbiturates and neuroleptics, the effect of the latter may decrease. When used together, it may change (increase or decrease) the effect of dantrolene or baclofen, so the doses of the drugs should be selected individually. Concomitant use with amantadine, ketamine, phenytoin and dextromethophan should be avoided due to an increased risk of developing psychosis. Plasma concentrations of cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine may increase when taken simultaneously with memantine. It is possible that hydrochlorothiazide levels may decrease when taken concomitantly with memantine. It is possible that the INR (international normalized ratio) may increase in patients taking oral anticoagulants (warfarin). Memantine may increase the excretion rate of hydrochlorothiazide. Concomitant use with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires careful monitoring of patients.

special instructions

Patients with Alzheimer's disease in the stages of moderate to severe dementia usually have impaired ability to drive vehicles and operate complex machinery. In addition, memantine may cause a change in the reaction rate, so patients should refrain from driving vehicles or operating complex machinery. Prescribe with caution to patients with thyrotoxicosis, epilepsy, convulsions (including a history), simultaneous use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan), the presence of factors that increase urine pH (sudden change of diet, for example, switching to vegetarianism, copious intake of alkaline gastric buffers), severe urinary tract infections, myocardial infarction (history), heart failure functional class III-IV (NYHA classification), uncontrolled arterial hypertension, renal failure, liver failure.

Dispensing conditions in pharmacies

On prescription

Expert advice

• One of two medications recommended for severe Alzheimer's disease;
• The action of memantine is similar to the natural inhibition of NDMA receptors by magnesium, so memantine is a kind of “artificial magnesium.”
• Theoretically, memantine's NMDA antagonism is strong enough to reduce the excitation of glutamate receptors characteristic of Alzheimer's disease, but not strong enough to affect the use of glutamate for plasticity, learning and memory.
• Has a related structure to amantadine, which is also a weak NMDA antagonist
• Memantadine is well tolerated and rarely causes side effects
• The consequences of 5-HT3 receptor antagonist activity have not been studied, but this may be why so few gastrointestinal side effects are observed [1]