Natural product For treatment of mild and moderate dementia

NIVALIN (GALANTAMINE)

Excessive Decurarizing Drug

Nivalin is an original phytopreparation developed by Sopharma's own research team and produced with an original technology for extraction of the alkaloid Galantamine from the bulbs of the plant snowdrops (Leucojum aestivum). Galantamine is the active ingredient in Nivalin.

Galanthamine hydrobromide (Nivalin, Sopharma AD, Bulgaria) is an orally and parenterally active reversible cholinesterase inhibitor which increases postsynaptic membrane susceptibility to acetylcholine.

In 1956 in Sofia, the pharmacologist D. Paskov suggested and L. Ivanova extracted an alkaloid base from the leaves of the plant Galanthus nivalis L. that they named galanthamine. In the form of hydrobromide salt it is commercially available as a registered product under the trade name NIVALIN

Galantamine formula

4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro-[3a,3,2,-ef][2]-benzazepin-6-ol

NIVALIN (GALANTAMINE) MECHANISM OF ACTION

Nivalin is competitive reversible inhibitor of Acetylcholinesterase (AChE) and prolongs the hydrolysis of endogenous mediator acetylcholine, thereby increasing its accumulation in the choline sensitive postsynaptic membranes.

Adaptation of nicotine cholinesterase transmission for account of the blockage of AChE and the sensibilization of nicotine acetylcholine receptors (nAChR).

ANTICHOLINESTERASE ACTIVITY

Nivalin inhibits reversibly brain, erythrocytic, muscle and serum cholinesterase. Its effect on brain cholinesterase is 10-12 times as potent, compared to physostigmine, since Nivalin crosses the blood-brain barrier.

  • Nivalin increases the intensity of nerve impulses leading to the muscle tissues, increases muscle contractions and their duration.
  • Nivalin antagonizes the effect of nondepolarizing neuromuscular blocking drugs. The antagonistic effect develops 20-30 s following parenteral administration and continues 30 to 60 minutes.
  • Nivalin stimulates the frequency and tone of the gastrointestinal muscle contraction.
  • Nivalin possesses mild hypotensive effect when administered in small or medium doses and in higher doses has two-phase action.

NIVALIN IN NEUROLOGY NIVALIN IS APPLICABLE IN:

  • Poliomyelitis (immediately after the febrile period and during the recovery and residual period.
  • Neuritis, myopathies, myasthenia, progressive muscular dystrophy, cerebral paralysis in childhood, cerebral palsy in neonates. Enuresis nocturna.
  • Residual paresis following haemorrhagic stroke.
  • Alzheimer's disease in light and medium stages.

NIVALIN IS APPLICABLE AS WELL IN:

  • To abolish the effects of nondepolarizing neuromuscular blockers and to treat postoperative paresis and bladder complications.
  • In some forms of impotence.
  • In mental retardation.
  • In poisoning with morphine and its analogues.
  • In functional diagnostics of the gastrointestinal tract (cholecystography and cholangiography.
  • In electrophoresis in neuritis of the auditory, facial and other nerves; neuritis, neuropathy, endarteritis obliterans, angioneurosis, acrocyanosis, dyshidrosis and neurodermitis.

RECOMMENDED DOSAGE SCHEMES:

  Ampoules Tablets
Age Appropriate doses Appropriate doses
From 1 to 2 years of age: 0.25  -  1.0 mg  
From 3 to 5 years of age: 0.50  -  5.0 mg  
From 6 to 8 years of age: 0.75  -  7.5 mg 5 - 10 mg
From 9 to 11 years of age: 1.00 - 10.0 mg 5 - 15 mg
From 12 to 15 years of age: 1.25 - 12.5 mg 5 - 25 mg
Over 15 yeas of age of age: 12.50 - 15.0 mg 10 - 40 mg

A treatment course continues for 1 - 2 months and in degenerative diseases of the Central Nervous System up to one year.

Nivalin is a preparation with low toxicity, soft and stable action and possesses wide spectrum of application for therapeutic purposes.

Nivalin is very well tolerated and despite that fact should not be prescribed in conditions of bronchial asthma, bradycardia, angina pectoris, heart failure, epilepsy, hyperkinetic dyskinesia.

SOPHARMA OFFERS NIVALIN IN THE FOLLOWING FORMS:

Nivalin products

Ampoules of 1 ml in the concentrations of 1 mg; 2.5 mg; 5 mg and 10 mg

Tablets in concentrations of 5 mg in package of 60 count and 10 mg in package of 20 count.

Composition

Galantamine hydrobromide — 0.10%, 0.25%, 0.50% and 1% solution in in ampoules of 1 ml; 1% injection solution in vials of 5 ml (multidose package); 1% solution collyriurm in vials of 10 ml; and tablets of 1, 5 and 10 mg.

Action

Nivalin, isolated from Galanthus nivalis var. gracilis (snowdrop), is an alkaloid with anticholinesterase action – inhibits the activity of cholinesterase, stabilizes acetylcholine, exhibits cholinomitetic effect. It facilitates the transmission of nerve impulses in the region of the neuromuscular synapses and the synapses of the central and vegetative nervous system. It increases the intensity of the reflex centers of the spinal cord, medulla oblongata and cerebral cortex, i.e. influences all links of the reflex arc: receptors, reflex centers, vegetative ganglia and neuromuscular junctions. Increases the tonus, intensifies its influence upon smooth and striated musculature and influences favorably the glands secretion. Nivalin exerts anticurare effect only towards the non-depolarizing muscle relaxants (those of the pachicurare group with concurrent action – d-tubocurarine, galamine, etc.) and shows potentiating influence in regard to the depolarizing muscle relaxants (succinylcholine, etc.).

Its action is antagonistic to morphine and its structural analogs, mainly inhibits their influence on the respiratory center. On instilling Nivalin collyrium in the conjunctival sac, it causes contraction of the pupil and decreases the raised intraocular tension. The preparation does not bring about abruptly expressed spasm of accommodation.

Effect

Pharmacologic properties - near to the Physostigmine and Neostigmine. It acts as a powerful reversible inhibitor of the cholinesterine and increases the sensibility of the receptors to the acetylcholine. It facilitates the conduction of the ebullience of the neuromuscular synapses and recuperates the neuromuscular conduction, when blocked by not-depolarizing neural muscular blockers. The Nivalin penetrates through the hematoencephalic barrier, facilitates the conduction of the CNS—impulses and enhances the excitation processes. It enhances the tonicity of the smooth musculature and enhances the secretion of the alimentary and perspiration glands, induces eye pupil contraction. It acts as antagonist towards the suppressing influence on the respiratory centre of the morphine and of its structural analogues. An oral form of Nivalin, suitable to be applied for children having affect on the central nervous system, as a result of generic traumas, infections etc. and as supporting therapeutics in durable treatment of children and adults in the intervals of the injection courses - for myasthenia, progressive muscle atrophy etc.

Pharmacokinetics

The Nivalin is resorbed very quickly. The therapeutic plasma concentrations are reached 25-30 minutes after the peroral application and are maintained up to five hours.

Contraindications

Bronchial asthma, bradycardia, stenocardia, cardiac decompensation, epilepsy, hyperkinesias.

Indications

Poliomyelitis – immediately after the fall of temperature, as well as in the recuperative and residual period; neuritis (especially in facial neuritis), radiculitis, radiculoneurities, polyneuritis, spastic pareses and paralyses and other sequelae of lesions of vascular, inflammatory, toxic and traumatic origin (cerebral apoplexy, meningitis, meningoencephalitis, myelitis, etc.; myopathies – myasthenia gravis pseudoparalytice, progressive muscular atrophy; consequences of diseases of the cerebrum vessels; motional and sensory violations, connected with diseases and traumatic damages of the nervous system; as anticurare means in anesthesiology; diseases with decreased tone of the smooth musculature of the urinary bladder and the gastrointestinal tract. As antidote, in morphine poisoning; in ophthalmology – mainly pronary glaucoma (better results are achieved in its congestive form, especially in acute stage); secondary glaucoma (favorable results are achieved only in separate cases).

Application and dosage

Nivalin is applied subcutaneously:

  • For adults: 2.5 – 25 mg daily
  • For children, according to age as follows:
  • From 1 to 2 years of age: 0.25 – 1 mg (= 0.1 – 0.4 ml of 2.5% solution)
  • From 3 to 5 years of age: 0.5 – 5 mg (= 0.2 – 2 ml of 2.5% solution)
  • From 6 to 8 years of age: 0.75 – 7.5 mg (= 0.3 – 3 ml of 2.5% solution)
  • From 9 to 11 years of age: 1 – 10 mg (= 0.4 – 4 ml
  • of 2.5% solution)
  • From 12 to 15 years of age: 1.25 – 12.5 mg (= 0.5 – 5 ml of 2.5% solution)

The indicated doses may in some cases be exceeded, but strictly individually, depending on the tolerance to the preparation and to the severity and duration of the disease. That optimum dose (not always the maximum one) should be determined, which leads to the best therapeutic effect. The tolerance to Nivalin in infancy is great.

The maximum dose for adults may in some cases be applied to bigger children.

The treatment should always begin with the smallest dose, which is gradually increased. When higher curative doses are reached, they are divided into 2 – 3 separate administrations. The course of treatment lasts 50 – 60 days. After an interval of 1 t 1.5 months the therapeutic course may be repeated 2 – 3 times. It is recommended to combine Nivalin treatment with physiotherapeutic procedures (massage, therapeutic exercise, etc.), which should be conducted 1 to 1 ½ hours after Nivalin injection. As anticurare means Nivalin is applied intravenously in the following dosage:

  • For adults: 10 – 40 mg (2 – 8 tablets of 5 mg) daily
  • For children:
  • From 1 to 2 years of age: 0.5 – 3 mg (1/2 to 3 tablets of 1 mg) daily
  • From 3 to 5 years of age: 1.25 – 7.5 mg (1/4 to 1 ½ tablets of 5 mg) daily
  • From 6 to 8 years of age: 5 – 12.5 mg (1 – 2 ½ tablets of 5 mg) daily
  • From 9 to 11 years of age: 5 – 15 mg (1 – 3 tablets of 5 mg) daily
  • From 12 to 15 years of age: 5 – 25 mg (1 – 5 tablets of 5 mg) daily

The daily dose is divided into 2 – 3 portions, while in the first 4 – 5 days the minimum initial dose is applied two times daily – in the morning and at noon after meal; in case of myasthenia gravis, the dosage is dividied into 3 portions – morning, noon and at the end of the day. Then the daily dose is increased to the optimal one. This indicated doses may in some cases be exceeded, depending on the tolerance of the preparation and the received effect of the treatment. The tablets should be taken 1 hour after meal. The course of treatment should last 50 – 60 days. The treatment of patients with myasthenia should be carried out strictly individually. After the optimum trating effect is reached, it is recommended to decrease the daily dose so that the minimum dose should be found, which maintains the therapeutic effect. Some days the patient may not take the preparation.

In light cases, only tablets are administered; in severe cases, in the intervals between the treatment with injections, the tablets are used.

In ophthalmology – Glaucoma 1 – 2 drops of the collyrium in the eye twice or three times a day in the interparoxysmal period.

In the acute period – a continual Nivalin bath on the eye. May be applied in combination with pilocarpine.

Side effects

Increased salivation, perspiration, nausea, vomiting, dizziness, rarely bradycardia. The dose is tehn reduced to the one, which does not cause side effecs, or the treatment is discontinued for 2 – 3 days after which lower doses are applied. If necessary as antidote may be used atropine, or ganglioplegics and myorelaxants. In collyrium – insignificant reddening of the conjunctiva and feeling of light itching may occur.

Packing

Boxes of 10 and 100 ampoules of 0.10, 0.25, 0.50 and 1% solution of 1 ml; and 1% solution – 5 ml for intravenous application.

Package with 20 and 50 tablets of 1, 5 and 10 mg.

Vials of 10 ml solution – 1% collyrium.

Galantamine Hydrobromide Substance

DESCRIPTION: The product is an alkaloid extracted from the tuberous plant Leucojum aestivum L. from the Amaryllidaceae family. It is manufactured as galanthamine hydrobromide. Galanthamine bromide substance is used in the manufacturing of the medication Nivalin, which is a strong (reversible) cholinesterase inhibitor, increasing the susceptibility of the organism to acetylcholine.

It facilitates the transmission of impulses in neuromuscular synapses and restores neuromuscular transmission. The drug crosses the hematoencephalic barrier and in proper doses facilitates the transmission in the synapses of the central nervous system, and enhances the excitation processes. It enhances the tone of the smooth muscles and intensifies the secretion of the gastric and sweat glands.

MOLECULAR MASS: 368.28 (hydrobromide) and 287.36 (base)

PYSICO-CHEMICAL INDICES OF THE FINISHED PRODUCT

Appearance Fine crystalline powder
Color White or almost white
Odor None
Solubility  
in water Poorly soluble
in 95% alcohol Practically insoluble
in chloroform Practically insoluble
in ether Practically insoluble
Specific rotation [α] 20D solution with concentration of 2.0 g/100 ml (°) From -90.0 to -100.0
Sulphates content (mg/g) Not more than 1.0
Sulphate ash (%) Not more than 1.0
Heavy metal content (mg/g) Not more than 20.0
Weight loss on drying (mg/g) Not more than 10.0
Galanthamine bromide content (%)  
Calculated as dry substance 98.0 - 100.5
Microbial content  
Total microorganisms (number/g) Not more than 10 -3
Moulds and yeast (number/g) Not more than 10 -2
Enterobacteriaceae, Ps. Aeruginosa, St. aureus Not allowed

SUPPLIED: The substance is filled in polyethylene bags of 2 kg and placed in cardboard barrels.

QUALITY: Bulgarian State Standard

EXPIRY: 5 YEARS

MEDICINAL FORM AND PACKAGE:

NIVALIN original Bulgarian patented medicine

  • Ampoules of 1 mg/ml; 2.5 mg/ml; 5 mg/ml and 10 mg/ml in packs of 10, 50 and 100
  • Syrup of o.5 mg/ml in bottles of 125 ml
  • Tablets of 1 mg and 5 mg in packs of 50 and 10 mg in packs of 20.

Contact Us

We'd really love to hear from you so why not drop us an email and we'll get back to you as soon as we can.

Back to Top
Back to Top!
Copyright © 2014 - 2015 Bulgarian Pharmaceutical Group Ltd./BiogenicStimulants, Inc. All rights reserved.