Carbamazepine 200mg pills №40

Tradename:

CARBAMAZEPIN

International non-proprietary name:

carbamazepine

Dosage Form:

pills

Composition

One pill contains:

active ingredient - carbamazepine 200 mg;

excipients: potato starch - 80.5 mg, colloidal silicon dioxide (aerosil) - 16.4 mg, talc - 3.1 mg, Magnesium stearate - 3.1 mg, povidone (polyvinylpyrrolidone) - 14.4 mg, polysorbate ( tween-80) - 2.5 mg.

Description: tablets of color, white or white with a yellowish shade, a flat-cylindrical form with risky and a facet.

Pharmacotherapeutic group:

antiepileptic drug.

Pharmacological properties:

Pharmacodynamics:

Carbamazepine is a derivative of dibenzoazepine and has antiepileptic, neurotropic, psychotropic and antidiuretic effects.

As an antiepileptic agent, it stabilizes the membranes of overexcited neurons, suppresses the serial discharges of neurons and reduces the synaptic transmission of excitatory impulses. This action is achieved, presumably, due to the blockade of sodium channels, as a result of which sodium-dependent action potentials are prevented from arising in depolarized neurons. Reduces the release of the neurotransmitter glutamate.The psychotropic effect of carbamazepine appears to be due to inhibition of dopamine and norepinephrine metabolism.

Reduces the frequency of attacks, anxiety, depression, irritability and aggressiveness in patients with epilepsy. The effect on cognitive function in patients with epilepsy is variable. Prevents paroxysmal pain with neuralgia. When alcohol withdrawal syndrome increases the threshold of convulsive readiness, reduces increased nervous irritability, tremor, gait disturbances. It is used to treat affective disorders as an antipsychotic and normo-chemical agent. With diabetes insipidus reduces diuresis and thirst.

Pharmacokinetics:

Absorption is slow, but quite complete (food intake does not significantly affect the rate and extent of absorption). After a single dose, the maximum plasma concentration is reached after 12 hours. Equilibrium plasma concentrations of the drug are reached in 1-2 weeks. Among patients there are significant individual differences in the values ​​of equilibrium concentrations in the therapeutic range. Communication with proteins of a blood plasma makes 70 - 80%. The concentration of unchanged carbamazepine in the cerebrospinal fluid and saliva is proportional to the amount of active substance not bound to proteins (20–30%). Concentration in breast milk is 25–60% of that in plasma. It penetrates the placental barrier.

It is metabolized in the liver, mainly along the epoxy pathway with the formation of metabolites: active - carbamazepine-10,11-epoxide and low-active - 9-hydroxy-methyl-10 carbamoyl acridane.The main isoenzyme providing biotransformation of carbamazepine to carbamazepine-10,11-epoxide is the cytochrome P450 isoenzyme 3A4. The content of carbamazepine-10,11-epoxide is about 30% of the level of carbamazepine in the plasma. Biotransformation of carbamazepine-10,11-epoxide to carbamazepine-10,11-transdiol occurs through the microsomal enzyme epoxide hydrolase. Another pathway of carbamazepine metabolism is the formation of various monohydroxylated derivatives, as well as N-glucuronides. The average half-life after a single dose is on average about 36 hours (varies from 25 to 65 hours), after repeated use - 16-24 hours. In patients receiving additional other antiepileptic drugs that induce liver enzymes, an average of 9-10 hours. mainly in the form of inactive metabolites in the urine (approximately 70%) and feces (approximately 30%). About 2% is excreted in the urine as unchanged carbamazepine and 1% as carbamazepine-10,11-epoxide.

In children, due to the faster elimination of carbamazepine, it may be necessary to use higher doses of the drug per kilogram of body weight as compared with adults.

There is no evidence that the pharmacokinetics of carbamazepine varies in elderly patients. There are no data on the pharmacokinetics of carbamazepine in patients with impaired renal or hepatic function.

Indications:

• Epilepsy (monotherapy or in combination therapy):

- complex and simple partial seizures (with loss or without loss of consciousness) with or without secondary generalization;

- generalized tonic-clonic seizures.Mixed forms of epileptic seizures.

• Acute manic states and supportive treatment of bipolar affective disorders in order to prevent exacerbations or reduce the severity of clinical manifestations.
• In the treatment of alcohol withdrawal syndrome.
• Neuralgia of the trigeminal nerve (idiopathic, with multiple sclerosis), idiopathic neuralgia of the glossopharyngeal nerve.
• Pain syndrome in diabetic neuropathy.
• Polyuria and polydipsia of neurohormonal nature with diabetes insipidus.

Contraindications:

• Hypersensitivity to any of the components of the drug or chemically similar drugs (tricyclic antidepressants),
• atrioventricular block,
• oppression of bone marrow hematopoiesis in history,
• hepatic porphyrias,
• simultaneous administration of monoamine oxidase inhibitors (hereinafter MAO inhibitors) and within 2 weeks after their withdrawal,
• breastfeeding period.

Use with caution when: low white blood cell or platelet count; mixed forms of epileptic seizures, including absence; in old age; with cardiac, hepatic, or renal failure; increased intraocular pressure; breeding hyponatremia; hypothyroidism; prostatic hyperplasia; pregnancy (increased risk of developing fetal abnormalities, including malformations).

Dosage and administration:

Inside, regardless of food intake with a small amount of liquid.

Epilepsy: whenever possible, carbamazepine should be given as monotherapy. The treatment begins with a small daily dose, which is subsequently slowly increased until the optimum effect is achieved. The addition of carbamazepine to already undergoing antiepileptic therapy should be carried out gradually.

For adults, the initial dose of 100-200 mg 1-2 times a day. Then the dose is slowly increased to 400 mg 2-3 times a day. The maximum daily dose of 2000 mg.

For children under the age of 5, the initial dose of 20-60 mg per day with an increase of 20-60 mg every two days. In children from 5 years, the initial dose is 100 mg / day, followed by an increase of 100 mg per week. Maintenance dose for children is 10-20 mg / kg of body weight per day for 2-3 doses. To ensure accurate dosing, in children under 5 years old, it is necessary to use liquid oral dosage forms of carbamazepine.

Neuralgia of the trigeminal or glossopharyngeal nerves: the initial dose of 200-400 mg / day, then the dose is gradually increased by no more than 200 mg per day until the pain stops (on average, up to 600-800 mg), then reduced to the minimum effective dose. In the treatment of elderly patients, the initial dose of 100 mg 2 times a day.

Alcohol withdrawal syndrome: the average dose is 200 mg 3 times a day. In severe cases, in the first days, the dose can be increased to 400 mg 3 times a day. At the beginning of treatment, severe withdrawal symptoms are prescribed in combination with detoxification therapy, sedatives and hypnotics.

Polyuria and polydipsia for diabetes insipidus: The average dose for adults is 200 mg 2 - 3 times a day. In children, the dose is selected based on body weight and age.

Pain syndrome in diabetic neuropathy: 200 mg 2 - 4 times a day.

Acute manic states and supportive care for bipolar affective disorders: daily dose of 400-1600 mg (average daily dose of 200-600 mg) for 2-3 doses per day. In acute cases, the dose is increased fairly quickly. With maintenance therapy, the dose increase should be gradual and small.

Side effect:

Nervous system disorders: dizziness, ataxia, drowsiness, fatigue, headache, diplopia, accommodation disturbances, tremors, muscle dystonia, tics, eye, orofacial dyskinesia, oculomotor disturbances, dysarthria, horeoatetoidnye disorders, peripheral neuropathy, paresthesia, paresis, taste disturbances, neuroleptic malignant syndrome .

Mental disorders: hallucinations (visual or auditory), depression, anorexia, anxiety, aggressive behavior, agitation, disorientation, increased psychosis.

From the skin and its appendages: allergic dermatitis, urticaria, exfoliative dermatitis, erythroderma, systemic lupus erythematosus, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, photosensitization reactions, erythema nodosum and knotty, erythema, skin pigmentation disorders, purpura, acne, sweating, hair loss. Rare cases of hirsutism have been reported, but the causal relationship of this complication with the drug intake remains unclear.

From the hemopoietic system: leukopenia, thrombosis, eosinophilia

From the hepatobiliary system: increase of gamma-glutamine transferase, alkaline phosphatase, transaminase; hepatitis (cholestatic, parenchymal (hepatocellular) or mixed type), jaundice, granulomatous hepatitis, hepatic insufficiency.

From the gastrointestinal tract: nausea, vomiting, dry mouth, diarrhea, constipation, abdominal pain, glossitis, stomatitis, pancreatitis.

Hypersensitivity Reactions: multiorgan hypersensitivity of the delayed type with fever, skin rashes, vasculitis, lymphadenopathy, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function indicators (these manifestations occur in various combinations). Other organs (lungs, kidneys, pancreas, myocardium, colon) may also be involved. aseptic meningitis with myoclonus and eosinophilia; anaphylactic reaction, angioedema.

Since the cardiovascular system: intracardiac conduction disorders; decrease or increase in blood pressure, bradycardia, arrhythmia,atrioventricular block with fainting, collapse, congestive heart failure , worsening of ischemic heart disease, thrombophlebitis, thromboembolism.

On the part of the endocrine system and metabolism: edema, fluid retention, weight gain, hyponatremia and decrease in plasma osmolarity due to an effect similar to the action of antidiuretic hormone, which in rare cases leads to water intoxication (hyponatremia of dilution), accompanied by lethargy, vomiting, headache, disorientation and neurological disorders; increased prolactin levels, with or without galactorrhea, gynecomastia; a decrease in the concentration of triiodothyronine and thyroxin, an increase in the concentration of thyroid-stimulating hormone, which is usually not accompanied by clinical manifestations; disorders of bone tissue metabolism (decrease in Calcium concentration and 25-hydroxycolecalciferol in the blood plasma), which leads to osteomalacia; increasing cholesterol concentrations, including high-density lipoprotein cholesterol and triglycerides.

From the genitourinary system: interstitial nephritis, renal failure, albuminuria, hematuria, oliguria, azotemia, frequent urination, urinary retention, disorders of sexual function, impaired spermatogenesis.

From the senses: violations of taste, clouding of the lens, increased intraocular pressure, conjunctivitis; hearing impairment.

From the musculoskeletal system: arthralgia, muscle pain, muscle weakness, convulsions.

On the part of the respiratory system: hypersensitivity reactions characterized by fever, shortness of breath, pneumonitis or pneumonia.

Changing laboratory results: hypogammaglobulinemia. 

Overdose:

Symptoms

- central nervous system: depression of the central nervous system up to coma, disorientation, drowsiness, agitation, hallucinations, feeling of "fog" in front of his eyes, dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia replaced at hyporeflexia, convulsions, psychomotor disturbances, myoclonus, hypothermia , mydriasis;

- respiratory system: respiratory depression, pulmonary edema;

- cardiovascular system: tachycardia, decrease or increase in blood pressure, impaired cardiac conduction with expansion of the QRS complex, cardiac arrest;

- digestive system: vomiting, delaying the evacuation of food from the stomach, decreased motility of the colon;

- urinary system: urinary retention, oliguria or anuria, fluid retention, dilution hyponatremia;

- laboratory indicators: metabolic acidosis, hyperglycemia, increased muscle fraction of creatine phosphokinase, hyponatremia.

Treatment: no specific antidote. Gastric lavage, the appointment of Activated carbon (late evacuation of gastric contents can lead to delayed absorption for 2-3 days and recurrence of symptoms of intoxication), hospitalization, symptomatic therapy.Forced diuresis, hemodialysis, and peritoneal dialysis are ineffective (dialysis is indicated with a combination of severe poisoning and renal failure). It is recommended to conduct hemosorption on coal sorbents.

Interaction with other drugs:

Simultaneous use with CYP3A4 isoenzyme inhibitors may lead to an increase in plasma carbamazepine concentration. The combined use of CYP3A4 isoenzyme inducers can lead to the acceleration of carbamazepine metabolism and to a possible decrease in its plasma concentration. Canceling simultaneously administered CYP3A4 isoenzyme inducers may decrease the rate of biotransformation of carbamazepine and lead to an increase in the level of carbamazepine in the blood plasma. At simultaneous use with the drugs metabolized by CYP3A4 isoenzyme, induction of a metabolism and decrease in their concentration in plasma is possible.

Drugs that can increase the concentration of carbamazepine or carbamazepine-10,11-epoxide in plasma:

dextropa; ibn , terfenadine, loxapine, olanzapine , Quetiapine , isoniazid, viral protease inhibitors for the treatment of HIV infection (for example, ritonavir), acetazolamide, Verapamil ,diltiazem, Omeprazole , oxybutynin, dantrolen, ticlopidine, nicotinamide (in adults, only in high doses), possibly cimetidine, desipramine, primidone, valproic acid.

Drugs that can reduce the concentration of carbamazepine in plasma:

Felbamate, Metsuksimid, Oxcarbazepine, Phenobarbital, Fensuxid, Phenytoin, Phosphenytoin, Primidon, Prohabid, Theophylline, Aminophylline, Isotretinoin, Rifampicin, Cisplatin , doxorubicin ; herbal preparations containing St. John's wort are holed and, although the data are contradictory, it is also possible that clonazepam, valproic acid or valpromid.

Effect of carbamazepine on plasma concentration of drugs used as concomitant therapy:

Carbamazepine can reduce plasma concentrations or reduce or even completely neutralize the effects of the following drugs: methadone, Paracetamol , antipirin, tramadol, Doxycycline , oral anticoagulants (warfarin, fenprocumone, dicumarol, acenocoumarol), bupropion, tsitalopram, zyrodone, fumarol, acetocoumarolol, bupropion, tsitalopram, zyrodone, fumarol, dyumarol, acenokumarol, bupropion, tsitalopram, zyrophramone, fumacoline, fumarolin, doxycycline. , nortriptiline, clomipramine), clobazam, clonazepam, ethosuximide, felbamate, lamotrigine, oxcarbazepine, primidone, tiagabine, topiramate , valproic acid, zonisamide, itraconazole, praziquantel, tinib, clozapine, Haloperidol , bromperidol, olanzapine, quetiapine, Risperidone , ziprasidone employed in the therapy of HIV infection (indinavir, ritonavir, saquinavir), alprazolam; midazolam, theophylline,calcium channel blockers of the group of dihydropyridines (for example, felodipine), Digoxin , oral contraceptives (selection of alternative methods of contraception is necessary), glucocorticosteroids (for example, prednisolone, dexamethasone); cyclosporine, everolimus, levothyroxine sodium, estrogens, and / or Progesterone . There are reports that in patients receiving carbamazepine, the level of phenytoin in the blood plasma can both increase and decrease, and the level of mephenytoin increases (in rare cases).

Combinations to be taken into account:

May increase hepatotoxicity caused by isoniazid, in the case of simultaneous use with carbamazepine.

In the case of co-administration with levetiracetam , the toxic effect of carbamazepine may increase.

Combined use of carbamazepine and lithium or Metoclopramide , as well as carbamazepine and neuroleptic drugs (haloperidol, thioridazine) can lead to an increase in the frequency of unwanted neurological reactions (in the case of the latter combination - even with therapeutic concentrations of active substances in the blood plasma).

The simultaneous use of carbamazepine with some diuretics (hydrochlorothiazide, furosemide) can lead to hyponatremia, accompanied by clinical manifestations.

Carbamazepine may be antagonistic to the action of non-depolarizing muscle relaxants (for example, pancuronium bromide).In the case of the use of such a combination of drugs, it may be necessary to increase the dose of these muscle relaxants; Careful observation of patients should be carried out, since the cessation of the action of muscle relaxants is possible as soon as possible than expected.

Combined use with grapefruit juice can increase plasma carbamazepine levels.

Special instructions:

Before treatment, as well as periodically in the course of treatment, clinical blood tests should be carried out (including counting the number of platelets, reticulocytes, as well as serum iron concentrations), general urine tests and determining the level of urea in the blood. The drug has a weak anticholinergic activity. Therefore, in the case of the use of the drug in patients with elevated intraocular pressure, constant monitoring of this indicator is necessary.

It is recommended to periodically determine the concentration of carbamazepine in the blood plasma in cases of increased incidence of epileptic seizures, in the treatment of children, in pregnant women, if used as part of complex therapy, the development of pronounced side effects.

There are separate reports of male fertility disorders and / or spermatogenesis disorders. However, the causal relationship of these disorders with the drug intake has not been proven to date.

Hypersensitivity cross-reactions may occur between carbamazepine and phenytoin or oxcarbazepine.

During the period of treatment, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration of attention and quickness of psychomotor reactions.

At the time of therapy, it is necessary to abandon alcohol intake, since carbamazepine increases the inhibitory effect of alcohol on the central nervous system.

Storage conditions.

In a dry, dark place at a temperature not higher than 25 ° C.

Keep out of the reach of children.