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Atropin Biotika Injection 0,5mg, 1,0mg


1 NAME OF THE MEDICINAL PRODUCT 

                                    Atropine 0.5 mg Biotika 
                                    Atropine 1 mg Biotika

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
Active substance:         Atropine sulfate monohydrate 0.5 mg in 1 ml. 
                                   Atropine sulfate monohydrate 1 mg in 1 ml. 

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM 
Solution for injection 
Clear, colourless solution. 

4. CLINICAL PARTICULARS
4. 1 Therapeutic indications 

Antidote for poisoning by acetylcholinesterase inhibitors, premedication before general anesthesia, in acute heart attack to manage bradycardia-hypotensive syndrome, atrial flutter and a fibrillation with a slow ventricular response, bradycardia and bradycardic arrhythmia as a result of parasympatotonia or overdose of beta-sympatholytics. Auxiliary drug in overdose-induced bradyarrhythmia after digitalis glycosides. Acute extrapyramidal dyskinesia in the begining of neuroleptic treatment. It is used in combination with spasmoanalgesics and papaverine.

4.2 Posology and method of administration 
a) Dosage for children: 
In anesthesia for premedication of newborns up to  65 µg dose, 100 µg for infants, in children from 6 months to 1 year 200 µg is administered intramuscularly. For older children, the applied dose is 10-20 µg / kg of body weight. 
On hot days, and in febrile children the doses are lowered. 
In cardiological indications the recommended dosage is 0.01 to 0.02 mg / kg of body weight.
b) Dosage for adults: 
Atropine is administered subcutaneously or intramuscularly at a dose of 0.5 mg as a spasmolytic in combination with papaverine. 
The premedication in anesthesia, during surgery is administered 0.5 to 1 mg intramuscularly 30-40 minutes before exercise or 0,3 to 0,5 mg intravenously 5 minutes before induction of anesthesia. 
During cardiopulmonary resuscitation it is administered intravenously 0.5 mg in five-minute intervals to a total dose of 2 mg. 
In cardiological indications the doses shall be relatively higher from 0.5 to 1 mg intravenously, which can be increased to 2 mg. Lower doses could deepen bradycardia as a result of n. vagus irritation. 
In the poisoning with acetylcholinesterase inhibitors ,2 mg are administered intravenously and if insufficient it is necessary to repeat the dose at 5 minute intervals until atropin symptoms appear (redness, dry skin, mydriasis, tachycardia). 
The highest single dose is 1 mg, the maximum daily dose is 2 mg.

4.3 Contraindications 
Glaucoma especially angle closure glaucoma, prostatic hypertrophy, organic pyloric stenosis, hyperthyroidism, mucoviscidosis, tachycardia and tachycardic arrhythmia, increased intracranial and intraocular pressure, severe acid-base disturbances, hypoxia. 

4.4 Special warnings and precautions for use 
It is not recommended to be administered during febrile illness, especially in children, because of the blockade of sweating atropine can cause hyperthermia. Caution is needed in disorders of bladder, because high doses of atropine reduce motility of the urethra. Sinus bradycardia in sick sinus syndrome is refractory to atropine and its application may cause post-tachycardia asystole. 

4.5 Interactions with other medicinal products and other forms of interaction
Inappropriate is the combination of halothane and methoxyflurane, mutual antagonism is with fyzostigmine, neostigmine and pilocarpine. Anticholinergic effect is increased by the current application of some antihistamines, phenothiazines, tricyclic antidepressants, butyrophenones, amantadine, antiparkinsonian agents, quinidine and pethidine. Chlorprotixen potentiates the central effects of atropine and a risk of delirium. Caution is required during a simultaneous application of propanidide, because of peripheral vasodilation and hypotension. The combination of diazepam and clonidine leads to synergism. The effect of atropine is increased by concomitant treatment with calcium entry blockers (verapamil, nifedipine, nitrendipin, nimodipine). Atropine may affect the absorption of other drugs slowing the digestive tube passage and reducing stomach acidity. 

4.6 Pregnancy and lactation 
Teratogenic effect of atropine is not known. Drug safety in pregnancy has not been established. It penetrates the placental barrier. Fetal tachycardia might occur. It passes into breast milk and may affect infants (hyperpyrexia, convulsions). For these reasons, atropine is not recommended during pregnancy and lactation. 

4.7 Effects on ability to drive and use machines 
Atropine can cause obscure vision and impaired concentration. 

4.8 Undesirable effects 
Following therapeutic doses: depression of salivary gland secretion, mydriasis, accommodation disturbances, increased intraocular pressure, photophobia, tachycardia or arrhythmia, urinary retention, headache, constipation. 
Higher doses: the blockade of thermoregulation with hyperthermia, excitement, twitching and muscle cramps, hallucinations and loss of consciousness. 

4.9. Overdose 

Atropine with its toxicological characteristic belongs to the highly toxic and highly hazardous substances. There is a great variability in sensitivity to high doses of atropine and therefore the details concerning the minimum lethal dose vary. After intramuscular or intravenous administration, the minimum toxic dose is 28 µg per kg of body weight, other sources say the lethal dose is 15 mg. In oral administration the lethal dose is higher , from 100 mg to 1 g as mentioned in literature. 
Symptoms: Intoxication is manifested by strong decline in secretion of salivary and bronchial glands, by tachycardia, hyperventilation, hyperpyrexia, palpitations, dry and flushed skin, mydriasis to accomodation paralysis, visual, olfactory and auditory hallucinations. Symptoms of CNS stimulation are restlessness, confusion, excitation, ataxia, psychotic or paranoid reactions. Urinal and fecal retention, apathy and unconsciousness occur. 
Treatment: Is symptomatic, proper hydration of the patient is important. Hyperpyrexia is suppressed by cooling of the body, in breathing disorders artificial ventilation of lungs is needed. Mental excitation and spasms are reduced by administration of diazepam, phenothiazines are not suitable. In severe cases, treatment consists of administration of parasympathomimetic from the group of reversible cholinesterase inhibitors such as physostigmine at a dose of 1-4 mg intravenously. If necessary, it could be repeated at one-hour intervals. It is necessary to monitor the patient. 


5. PHARMACOLOGICAL PROPERTIES 

5.1 Pharmacodynamic properties 
Pharmacotherapeutic group: Parasympatolytikum. 
ATC code: A03BA01 

Mechanism of effect 
Atropine acts as a competitive antagonist of acetylcholine at muscarinic receptors. It reduces the secretion of salivary, sweat, gastric glands and respiratory glands. At therapeutic doses (0.4 to 0.6 mg)it  may cause transient bradycardia as a result of vagus nerve irritation. In higher doses, after the blockade of vagal effect on sinoauricular node,it  leads to tachycardia. It causes mydriasis and accommodation disturbances in the distance in the eye. It has a spasmolytic effect in smooth muscle. 

5.2 Pharmacokinetic properties 
After intravenous injection the onset of effect is in 30-90 seconds, after subcutaneous administration in 15-30 minutes, after intramuscular administration in 30-45 minutes. Plasma protein binding is 14-22%. Volume of distribution is 1.7 to 2.3 liters / kg. It crosses the placental and the blood-brain barrier well. 
Atropine is metabolised in the liver by microsomal monooxygenase to metabolites tropic acid and tropin (29%), esters of tropic acid and conjugates with glucuronic acid. Unchanged form (30-60%) of atropine and its metabolites are excreted renally (94% of the total dose per 24 hours). Renal plasma clearance is 660 ml / min and depends on renal blood flow. Elimination half-life is 2-3 hours in adults, in children may be extended to 6.9 +3.3 hours. There is a big individual variability. Elimination is prolonged in children younger than 2 years and in the elderly. 

6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients 
Excipients: sodium chloride, disodium edetate, water for injection 
Sodium content in the product: 3.572 mg / ml, corresponding to 0.155 mmol / ml. 

6.2 Incompatibilities 
Atropine after diluted in isotonic sodium chloride solution and 5% glucose solution is not stable for longer period of time. Do not administer with sodium bicarbonate solution. 

6.3 Shelf life 
5 years

6.4 Special precautions for storage 
Store at 10-25 ° C 

6.5 Nature and contents of container 
Clear glass, insert PVC, paper box 
Package size: 10 ampoules of 1 ml. 

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER 
BB Pharma Pod Višňovkou 1662/21, 140 00 Prague 4, Czech Republic 

8. MARKETING AUTHORISATION NUMBER(S) 
53/761/92-S/C (0.5 mg) 
53/762/92-S/C (1 mg) 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 Decebrer 14th, 1992 / March 4th, 2009

10. DATE OF REVISION OF THE TEXT
March 4th, 2009