Neurorubin Forte lactab, tablets N20 - Instructions

Pharmacological properties of the drug Neurorubin

B vitamins are components of enzyme systems that regulate protein, lipid and carbohydrate metabolism. Each of the B vitamins plays a specific biological role. Their presence in the body in a balanced amount is necessary for the normal functioning of metabolism. The drug Neurorubin and Neurorubin-Forte are a combination of 3 vitamins in high doses: B1, B6, B12, which play an important role in the functioning of the nervous system. Each of these vitamins is necessary to ensure optimal metabolism in nerve cells. When high doses of vitamins are consumed simultaneously, they exhibit an analgesic effect. Thiamine mononitrate (vitamin B1) is absorbed in the small intestine, duodenum and jejunum. After ingestion, thiamine penetrates the intestinal mucosa and enters the liver through the portal vein system. After administration, some thiamine is absorbed in the liver. The main metabolites that are released when thiamine is taken (with minor amounts of unchanged thiamine) are thiamine carboxylic acid and pyramine (2,5-dimethyl-4-aminopyrimidine). Pyridoxine hydrochloride (vitamin B6) is rapidly absorbed in the intestine. In the body, pyridoxine is oxidized to pyridoxal and aminated to pyridoxamine. The condition for its functioning as a coenzyme is phosphorylation at the CH2OH group in the 5th position, that is, the formation of pyridoxal-5-phosphate (PALP). In the blood, 80% is associated with proteins. Pyridoxine preferentially accumulates in muscles. The main metabolite that is excreted is 4-pyridoxic acid. Cyanocobalamin (vitamin B12). Normally, the absorption of cyanocobalamin is limited and depends on the concentration of intrinsic Castle factor. Some of the vitamin is absorbed in the free state, but the majority is absorbed after binding to intrinsic Castle factor. After absorption from the gastrointestinal tract, vitamin B12 enters the blood serum. The accumulation of vitamin B12 occurs mainly in the liver. The half-life from serum is approximately 5 days, from liver tissue - approximately 1 year.

Neurorubin solution d/in. in amp. 3ml per bl. in pack №5x1

Description

Transparent red solution in brown glass ampoules.

Main active ingredient

Multivitamin

Release form

Solution

Dosage

text

special instructions

Due to the lack of studies regarding drug compatibility, Neurorubin cannot be mixed with other drugs.

Pharmacological properties

Pharmacodynamics

B vitamins are most often part of enzyme systems that regulate the metabolism of proteins, fats and carbohydrates. However, each of the B vitamins performs a specific biological role. Their presence in the body in a balanced amount is necessary for the normal functioning of metabolism. Neurorubin combines high doses of three vitamins: B1, B6, B12, which play an important role in the functioning of the nervous system. Each of these vitamins is necessary to ensure optimal metabolism in nerve cells. In addition, high doses of these vitamins, when used, exhibit an analgesic effect. Neurotropic B vitamins have a beneficial effect on inflammatory and degenerative diseases of the nerves and locomotor system. In large doses, they not only have a substitutive effect, but also have a number of pharmacological effects: analgesic, anti-inflammatory, microcirculatory. Vitamin B1 in the form of thiamine diphosphate and thiamine triphosphate plays a key role in carbohydrate metabolism, being a coenzyme of pyruvate decarboxylase, 2-oxogutarate dehydrogenase and transketolase. In the pentose phosphate cycle, thiamine diphosphate is involved in the transfer of aldehyde groups. Vitamin B6 in its phosphorylated form (pyridoxal-5-phosphate) is a coenzyme of numerous enzymes, primarily involved in the metabolism of amino acids, as well as carbohydrates and fats. Vitamin B12 is essential for cellular metabolism, hematopoiesis and the functioning of the nervous system. It stimulates nucleic metabolism through the activation of folic acid. In large doses, cyanocobalamin has analgesic, anti-inflammatory and microcirculatory effects.

Pharmacokinetics

Water-soluble vitamins are completely absorbed in the body after intramuscular administration. The degree of absorption depends on the location of the bloodstream relative to the injection site. Cyanocobalamin (vitamin B12). After absorption, vitamin B12 binds in serum to specific B12-binding beta (transcobalamin) and B12-binding alpha1 globulin. Vitamin B12 accumulation occurs mainly in the liver. The half-life from serum is approximately 5 days, and from the liver - approximately 1 year. Thiamine hydrochloride (vitamin B1). Part of the absorbed thiamine takes part in the enterohepatic circulation. The main products of thiamine excretion are thiaminecarboxylic acid and pyramine (2,5-dimethyl-4-aminopyrimidine). At the same time, a small amount of thiamine is released unchanged. Pyridoxine hydrochloride (vitamin B6). In the body, pyridoxine is oxidized to pyridoxal or aminated to pyridoxamine. The condition for its functioning as a coenzyme is phosphorylation at the CH2OH group in the 5th position, that is, the formation of pyridoxal-5-phosphate (PALP). In the blood, approximately 80% of PALP is protein bound. Pyridoxine predominantly accumulates in muscles in the form of PALP. The main excretion product is 4-pyridoxic acid. Thiamine is absorbed in the small intestine by active transport. Its absorption is limited to 8-15 mg per day. To prevent vitamin B1 deficiency, its daily replenishment should be 1.3-1.5 mg per day in men, 1.1-1.3 mg in women. Thiamine is excreted in the urine. Pyridoxine, pyridoxal and pyridoxamine are absorbed very quickly and are converted to pyridoxal-5-phosphate. The main metabolite is 4-pyridoxic acid. The required daily amount of vitamin B6 depends on the intensity of protein metabolism; its deficiency is prevented in men with a daily dose of 2.3 mg per day, in women - 2.0 mg. Excreted by the kidneys. Vitamin B12 in the stomach during digestion is released from food and binds to intrinsic factor. The resulting complex is resistant to proteolytic enzymes. Having passed into the distal part of the small intestine, it interacts with specific receptors and then enters the systemic circulation, where it binds to transcobalamin. This complex enters the liver, bone marrow and other proliferating cells, where it is converted into the active form - adenosylcobalamin and methylcobalamin. Vitamin B12 penetrates the placenta. 1.5-3.5 mcg of vitamin B12 is supplied daily with food. If intrinsic factor is deficient, the absorption of vitamin B12 is impaired. The main place of deposition of vitamin B12 is the liver. The half-life is approximately 12 months. It is excreted in bile and, to a lesser extent, in urine.

Indications for use

Neurological disorders caused by a deficiency of vitamins B1, B6, B12, which cannot be eliminated by oral administration of the vitamins included in Neurorubin. Neurorubin is used in adults.

Directions for use and doses

One ampoule is used once a week. The injection is administered deep into the muscle of the upper outer quadrant of the gluteal region, slowly. The duration of treatment depends on the nature and course of the disease and is determined by the doctor. After 4 months of using the drug Neurorubin, the patient should be transferred to oral dosage forms. The drug is administered exclusively intramuscularly. If the drug is accidentally administered intravenously, the patient must be monitored by specialists on an outpatient or inpatient basis, depending on the severity of the symptoms that arise.

Use during pregnancy and lactation

Animal studies of the drug Neurorubin and clinical studies on the use of this drug in women during pregnancy have not been conducted. During pregnancy and breastfeeding, it is recommended to take daily vitamin B1 in a dose of 1.4-1.6 mg per day, vitamin B6 - 2.4-2.6 mg per day. Taking these doses can only be recommended if there is a deficiency of these vitamins. Administration of vitamin B6 in a dose of less than 25 mg per day during pregnancy and breastfeeding is safe. The ampoule contains 100 mg of vitamin B6, so the use of the drug during pregnancy is contraindicated. If it is necessary to use the drug during lactation, breastfeeding should be discontinued. Vitamins B1, B6, and B12 pass from the body into breast milk. High doses of vitamins B6 and B12 can suppress lactation.

Precautionary measures

The drug is administered exclusively intramuscularly. Long-term use of the drug (over 6 months) can cause the development of neuropathy. Intramuscular injections of vitamin B12 may cause anaphylactoid reactions in hypersensitive patients. Children. There is no experience in treating children with this drug, so the drug is not prescribed to children.

Interaction with other drugs

High doses of vitamin B6, such as those contained in Neurorubin, may reduce the therapeutic effect of levodopa on Parkinson's disease. Pyridoxine antagonists, such as isoniazid, cycloserine, penicillamine, hydralazine, may reduce the effectiveness of vitamin B6. Loop diuretics such as furosemide may decrease vitamin B1 concentrations.

Contraindications

The drug is not recommended for use in patients who are sensitive to one or more components, especially vitamins B1, B6, and B12. Children under 18 years of age. Indication of a history of epileptiform seizures.

Compound

active ingredients: 3 ml of solution (1 ampoule) contains: thiamine hydrochloride (vitamin B1) 100 mg, pyridoxine hydrochloride (vitamin B6) 100 mg, cyanocobalamin (vitamin B12) 1 mg; excipients: potassium cyanide 0.25 mg/3 ml, benzyl alcohol, water for injection.

Overdose

Vitamins B1, B6, and B12 have a wide range of therapeutic effects. The phenomena of overdose with proper use have not been known until now. a) Symptoms of intoxication A very high intravenous dose of vitamin B1 (more than 10 g) has a ganglion blocking effect on people and suppresses the transmission of excitation to nerve cells, similar to the action of curare, since thiamine binds to nicotinic cholinergic receptors. The phenomena of hypervitaminosis after taking large amounts of vitamin B1 for a month have not been described before. Vitamin B6, even in doses of 50 mg per day, with medium-term use, can cause severe irreparable neurotoxicosis. Hypervitaminosis, the phenomena of overdose or poisoning of vitamin B12 in humans were not previously known. b) Therapy for intoxication There are no special countermeasures for intoxication; Treatment should be carried out according to symptoms.

Side effect

Side effects are classified by frequency as follows: very often (? 1/10); often (? 1/100 to

Storage conditions

Store at a temperature of 2-8°C (in the refrigerator). Keep out of the reach of children. Shelf life: 3 years.

Buy Neurorubin solution d/in. in amp. 3ml per bl. in pack No. 5x1 in the pharmacy

Price for Neurorubin solution d/in. in amp. 3ml per bl. in pack №5x1

Instructions for use for Neurorubin solution d/in. in amp. 3ml per bl. in pack №5x1

Indications for use of the drug Neurorubin

Oral use: concomitant therapy for diseases of the nervous system, such as:

• neurotic pain in acute and chronic neuritis and polyneuritis;
• neuralgia, as well as toxic damage to the nervous tissue due to alcoholism, drug intoxication, and diabetic polyneuropathy.

Parenteral use: peripheral neuropathy of alcoholic origin, Wernicke-Korsakoff syndrome, diabetic polyneuropathy, beriberi (dry and wet forms); as an adjuvant for acute or chronic neuritis and polyneuritis, trigeminal neuralgia, cervicobrachial neuralgia, sciatica.

Use of the drug Neurorubin

Orally Take orally, before or during meals, without chewing, with a sufficient amount of water. The usual dose for adults is 1–2 tablets per day. The course of treatment is 4 weeks. Treatment can be continued at the discretion of the doctor. Parenteral In case of severe disease, the dose for adults is: at the beginning of use - 3 ml of solution (contents of 1 ampoule) IM daily or every other day until the severity of pain decreases; in the future - 3 ml of solution 1-2 times a week. For moderate disease, the dose for adults is 3 ml of solution 1–2 times a week. Injected intramuscularly into the outer upper quadrant of the gluteal muscle. The duration of treatment depends on the cause of the deficiency of B vitamins; treatment is continued until clinical recovery and/or normalization of laboratory parameters. During long-term therapy, clinical monitoring is carried out every 6 months.

Neurorubin Forte lactab, tablets N20 - Instructions

Compound

The main functional components are: thiamine hydrochloride (vitamin B1), pyridoxine (B6) and cyanocobalamin (B12).
Other ingredients: cellulose powder, hypromellose, pregelatinized starch, mannitol, microcrystalline cellulose, magnesium stearate and colloidal silica, titanium dioxide, macrogol 6000, erythrosine, talc and hypromellose.

Release form

The medicine is available in tablets. Supplied in packs of 20 pieces each.

pharmachologic effect

The Neurorubin vitamin complex contains water-soluble vitamins B1, B6, and B12. However, these vitamin compounds belong to the same group of beneficial substances that are known for their wide range of biological activities. In addition, each vitamin is responsible for various processes occurring in the human body.

Vitamin B1, for example, is actively involved in the metabolism of carbohydrates, fats and, in addition, proteins. In the absence of thiamine in the body, the level of pyruvic acid, as well as lactic acid, increases. Useful links in the process of transamination and deamination of essential amino acids.

Thus, vitamin B1 normalizes protein metabolism. It should be noted that the substance acts as a catalyst in the process of fat metabolism and the formation of fatty acids. Stimulates secretory function and intestinal motility. It also interacts with cell membranes in neurons and turns on ion channels.

Vitamin B6, like B1, is actively involved in the metabolism of proteins and fats, as well as in the synthesis of enzymes. This beneficial compound for the human body acts as a coenzyme in enzyme reactions. Pyridoxine stimulates the formation of myelin membranes of neurons, and is also involved in the metabolism of proteins and fats, the synthesis of hemoglobin and neurotransmitters at the synapses of the central and peripheral nervous system.

Cyanocobalamin plays an important role in protein metabolism and regulates the production of purines, nucleic acids and, in addition, amino acids. This compound, cyanocobalamin, is essential for the body because it affects the production of acetylcholine, as well as the myelination of neurons. In addition to this vitamin, the compound has a positive effect on the regeneration of nerve fibers and stimulates peripheral nerve structures in the production of impulses.

The substance has a hematopoietic effect on the human body. Regulates cholesterol levels and promotes erythropoiesis. Cyanocobalamin improves hematopoiesis and normalizes coagulation. Together, vitamins B1, B6 and B12 help normalize the functioning of the human nervous system; in addition, they have a positive effect on protein, lipid, fat and carbohydrate metabolism.

It is also worth mentioning the fact that the combination of vitamin compounds relieves pain in neurological diseases of various origins.

Pharmacokinetics

The pharmacokinetics of Neurorubin depends on the characteristic properties of drug-forming vitamin compounds.

Absorption of thiamine occurs after entering the intestines, jejunum and duodenum. A small amount of vitamin B1 is digested by the liver and becomes a useful active ingredient in the metabolism and breakdown of pyramine and thiamine carboxylic acid. Thiamine is excreted from the body through the kidneys and intestines, both unchanged and in the form of metabolites.

Pyridoxine hydrochloride is absorbed in the intestine and then metabolized in the body and breaks down into pyridoxamine, pyridoxal-5-phosphate and coenzyme pyridoxal (active metabolites of the vitamin compound).

Vitamin B6 is characterized by a close connection with proteins contained in plasma. The compound accumulates in living organisms in muscles, liver, and also in the organs of the nervous system. Pyridoxine is excreted from the body by the kidneys, as well as thiamine (B1) in the same composition or in the form of active metabolites.

With normal absorption of vitamin B12, beneficial links are metabolized and converted into adenosylcobalamin. The compound is excreted in bile and urine, and also combines in the liver.

Indications for use

Tablets are used for preventive purposes in conditions characterized by a lack of B vitamins, as well as in complex therapy in the treatment of diseases such as:

• polyneuritis;
• neuritis;
• neuralgia;
• poisoning Including alcohol;
• diabetic polyneuropathy.

Contraindications

Strict restrictions include:

• pregnancy;
• predisposition to allergies;
• breast-feeding;
• hypersensitivity to the composition of the drug;
• age up to 18 years.

Side effects

The following side effects may occur when taking Neurorubin Forte:

• vomit;
• increased concentration in the blood, disruption of transmyases;
• weakness;
• stomach bleeding;
• headache;
• increased irritability;
• causeless anxiety;
• dizziness;
• sensory neuropathy;
• tachycardia;
• circulation;
• pulmonary edema;
• itching;
• acne development;
• hives;
• skin rash;
• increased sweating;
• cyanosis;
• angioedema;
• anaphylactic shock.

Compatibility with other medications

Neurorubin cannot be combined with levodopa and altretamine, since the vitamin complex reduces the effectiveness of these drugs. To avoid increased toxicity of isoniazid, the drug and B complex vitamins should not be used simultaneously.

It should be noted that vitamin B1 antagonists are substances such as fluorouracil, as well as thiosemicarbazone. The absorption of Neurorubin Forte Lactab is reduced by drugs that have antacid properties and provide an enveloping effect.

Application and dosage

The tablets must be taken after or during meals, without chewing.

In adults, the average therapeutic dose range is 1-2 tablets per day. In general, treatment with Neurorubin lasts on average one month.

Overdose

To date, no cases of overdose have been reported.

special instructions

People with heart failure and angina pectoris should take this vitamin complex with extreme caution.

Use during pregnancy and breastfeeding

The appointment is contraindicated.

Impact on the ability to drive vehicles and operate machinery

No special precautions are required.

Terms of sale

As prescribed by the doctor.

Storage conditions

In a dry, cool place with limited access for children.

Side effects of the drug Neurorubin

Hypersensitivity. In patients with hypersensitivity, angioedema may occur. Allergic reactions are observed quite rarely. In isolated cases and under certain conditions, repeated intramuscular injections of preparations containing vitamin B1 can cause anaphylactic shock in patients with hypersensitivity. In these cases, corticosteroids and antihistamines can be used for treatment. Endocrine system. When taking the drug, the release of prolactin is inhibited. Nervous system. In some cases, a feeling of anxiety arose (in patients with hypersensitivity). When taking high doses of pyridoxine hydrochloride (500 mg/day) over a long period of time, isolated cases of reversible peripheral sensory neuropathy have been reported. The cardiovascular system. Isolated cases of tachycardia, circulatory collapse (in patients with hypersensitivity). Respiratory system. Isolated cases of cyanosis, pulmonary edema (in patients with hypersensitivity). Gastrointestinal organs. Nausea, bleeding from the gastrointestinal tract (in patients with hypersensitivity). Liver and gall bladder. High doses of the drug may lead to increased levels of glutamic oxaloacetic transaminase (SGOT) in the blood plasma. Leather. Reactions with itching and urticaria (in patients with hypersensitivity). High doses of the drug may cause acne. Pyridoxine hydrochloride may cause acne. General symptoms. Sudden sweating, feeling of weakness, dizziness.

Neurorubin injection solution 3 ml No. 5

Contraindications

Hypersensitivity to the components of the drug.

Vitamin B1 is contraindicated for use in allergic diseases.

Vitamin B 6 is contraindicated for use in case of peptic ulcer of the stomach and duodenum in the acute stage since it is possible to increase the acidity of gastric juice).

Vitamin B 12 is contraindicated for use in cases of erythremia, erythrocytosis, and thromboembolism.

Interaction with other drugs and other types of interactions

High doses of vitamin B6, such as those contained in Neurorubin™, may reduce the therapeutic effect of levodopa for Parkinson's disease.

Isoniazid toxicity may increase.

Vitamin B6 may reduce the effectiveness of altretamine.

Concomitant use with pyridoxine antagonists (for example, isoniazid, hydralazine, penicillamine or cycloserine), oral contraceptives may increase the need for vitamin B6.

The action of thiamine is inactivated by 5-fluorouracil, since the latter competitively inhibits the phosphorylation of thiamine to thiamine pyrophosphate.

Antacids slow down the absorption of vitamin B1.

Loop diuretics, such as furosemide, which inhibit tubular reabsorption, with long-term therapy can cause an increase in thiamine excretion and, thus, reduce its level.

Consumption of drinks containing sulfites (for example, wine) increases the degradation of thiamine.

Features of application

The drug should not be administered intravenously.

Intramuscular injections of vitamin B 12 may cause anaphylactoid reactions in patients with hypersensitivity.

Parenteral administration of vitamin B 12 may temporarily interfere with the diagnosis of funicular myelosis or pernicious anemia.

Long-term use of vitamin 6 (more than 6-12 months) in doses greater than 50 mg daily or in doses greater than 1000 mg per day (more than 2 months) can lead to reversible peripheral sensory neuropathy. If symptoms of peripheral sensory neuropathy (paresthesia) occur, the dose of the drug must be adjusted and, if necessary, discontinued.

Since Neurorubin TM contains vitamin 6, it should be used with caution in patients with a history of gastric and duodenal ulcers, with severe impaired renal and liver function.

Patients with neoplasms, with the exception of cases accompanied by megaloblastic anemia and vitamin B12 deficiency, should not use the drug.

The drug is used for severe or acute forms of cardiac decompensation and angina.

Use during pregnancy or breastfeeding.

There are no clinical studies of Neurorubin™ treatment in animals or women during pregnancy.

The drug is prescribed only after a careful assessment of the benefit-risk ratio, since there is insufficient data on the safety of the drug during pregnancy.

Vitamins B1, B6 and B12 are excreted into breast milk. High concentrations of vitamin B6 may suppress milk production. Studies on the degree of secretion of vitamins into breast milk have not been conducted. The decision to discontinue breastfeeding or use of the drug must be made taking into account the need for the drug for the mother. If it is necessary to use the drug, you should stop breastfeeding for this period.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

The drug does not affect the ability to drive vehicles or operate machinery.

If dizziness occurs during treatment, you should refrain from driving vehicles and operating machinery.

Directions for use and doses

For intramuscular administration.

In severe (acute) cases, 1 ampoule per day until acute symptoms subside.

After easing symptoms or in cases of moderate severity, 1 ampoule 1-3 times a week.

To maintain or continue the course of injection therapy or to prevent relapse, it is recommended to use the drug Neurorubin ™ for Laktab, film-coated tablets.

Do not exceed the recommended daily dose.

The duration of treatment depends on the nature and course of the disease and is determined by the doctor.

Application technique.

To open the ampoule:

• hold the ampoule up with the marking in the form of a dot;
• shake the ampoule until the liquid reaches the bottom;
• break off the ampoule head above the marking.

Children

There is no experience in treating children with this drug, so it should not be prescribed to children.

Overdose

In case of overdose, the symptoms of side effects increase.

Vitamin B1: has a wide therapeutic range. Very high doses (more than 10 g) exhibit a curare-like effect, suppressing the conduction of nerve impulses.

Vitamin B6: has very low toxicity.

Excessive use of vitamin 6 in doses greater than 1 g per day for several months can lead to neurotoxic effects.

Neuropathies with ataxia and sensory disorders, cerebral spasms with EEG changes, as well as in some cases hypochromic anemia and seborrheic dermatitis have been described after administration of more than 2 g per day.

Vitamin B12: after parenteral administration (in rare cases, after oral administration) of the drug in doses exceeding the recommended ones, allergic reactions, eczematous skin disorders and a benign form of acne were observed. With long-term use in high doses, disturbances in the activity of liver enzymes, pain in the heart, and hypercoagulation are possible.

Adverse reactions

From the immune system: hypersensitivity reactions, including angioedema, anaphylactoid reactions, anaphylactic shock, mainly in patients with hypersensitivity.

From the endocrine system: inhibition of prolactin release.

From the nervous system: anxiety; long-term use (more than 6-12 months) of pyridoxine hydrochloride (vitamin B 6) in doses of more than 50 mg daily can lead to peripheral sensory neuropathy, nervous agitation, malaise, headache, dizziness.

From the cardiovascular system: tachycardia, circulatory collapse, mainly in patients with hypersensitivity.

From the respiratory system: cyanosis, pulmonary edema, mainly in patients with hypersensitivity.

From the gastrointestinal tract: gastrointestinal disorders, including vomiting, diarrhea, abdominal pain, increased acidity of gastric juice, nausea, bleeding from the digestive tract, mainly in patients with hypersensitivity.

From the digestive system: high doses may lead to increased levels of glutamine aspartate aminotransferase (AST) in the blood serum.

From the skin and subcutaneous tissue: itching, urticaria, mainly in patients with hypersensitivity.

High doses of the drug can lead to acne. Pyridoxine hydrochloride may cause worsening of acne vulgaris or the appearance of acne.

General reactions: reactions at the injection site, increased sweating, weakness, feeling of a “lump” in the throat.

Best before date

3 years.

Storage conditions

Store at a temperature of 2 to 8 ° C (in the refrigerator). Keep out of the reach of children.

Incompatibility

Due to the lack of drug compatibility studies, Neurorubin™ cannot be mixed with other drugs.

Package

3 ml per ampoule; 5 ampoules per box.

Vacation category

On prescription.

Drug interactions Neurorubin

Because pyridoxine hydrochloride stimulates the decarboxylation of L-dopamine (levodopa) and may reduce the therapeutic effect of this drug in the treatment of patients with Parkinson's disease, the simultaneous use of these drugs should be avoided. The toxicity of isoniazid may increase when used in combination. Thiosemicarbazone and fluorouracil reduce the effectiveness of vitamin B1, being its antagonists. Antacids slow down the absorption of vitamin B1. Vitamin B6 may reduce the effectiveness of altretamine.