ACSERA Scorpion Antiserum

ACSERA Scorpion Antiserum

SUMMARY OF PRODUCT CHARACTERISTICS (SmPC)
1. NAME OF THE MEDICINAL PRODUCT
ACSERA 5 mL enjektabl solution concentrate including vial

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Active substance:
Immunoglubulin F(ab’)2 fragments against
Androctonus crassicauda scorpion venom (Equine) At least 100 neutralization unit

Excipients:
Sodium chloride 42,5 – 47,5 mg
For excipients see section 6.1

3. PHARMACEUTICAL FORM
Solution for injection.
Whiffed, clear, almost colourless or faintly yellow, colored liquid solution.

4. CLINICAL PARTICULARS
4.1 Therapeutic Indications
ACSERA is indicated in prevent to envenomation caused scorpion sting and following
possible deaths.

4.2 Posology and method of administration
Posology/frequency and time of application:
Dose is determined by doctor according to severity of poisoning. Maximum 10 vials are used.

Degree 0
If there is not any local or systemic indications, treatment no need.

Degree I (mild severity cases)
If observed in injection site as local indications, ache / paresthesia, cold extremities, sweat,
restlessness, hypotension; 1-2 vials are applied by intramuscular or subcutaneous way. If not
see recovery, this dose may repeat after 1-2 hours.

Degree II (mean severity cases)
If observed degree I indications, tachycardia, gallop rhythm, sickness and vomiting; 1-2 vials
are applied by intramuscular or subcutaneous way. If not see recovery, this dose may repeat
after 1-2 hours.

Degree III (severity cases)
If observed degree II indications, neuromuscular function disorder (cranial, autonomic or
somatic); 5 vials must applied by intravenous way for 30 minutes by as 1/10 diluting with
saline. If not see recovery, this dose may repeat after 1-2 hours.
Also last time between scorpion stings with treatment is long or creepy site is head, neck or
shoulder; amount of dose need increase.

Application form:
ACSERA is applied by intravenous, subcutaneous or intramuscular injections.
For treatment, the content of vial of antiserum (5 mL) should be applied by intramuscular
route.
The most important rule while applied the antiserum is injected to sting area in as soon as
possible for urgently prevent give to blood circulation.
The antiserum is applied very slowly by intravenous way for in cases of severity poisoning,
passed long time from scorpion sting and in question of life threat.

Addition information about special populations:
Kidney / liver failure
There is no data.

Pediatric population:
Plasma toxin concentrate of children is higher than health and adult a person because their
body mass is less.
Also immunity system of children already not completion. Therefore excretion capacity of
venom from children (more long biological half life) more than health adult a person.
Addition to this information, other disease as pneumonia which will be deteriorated resulted
toxic effects should be observed too. For this reason children are more affected from scorpion
poison and antiserum treatment should be started as far as possible. Apply to dose may be
increase folded or more according to severity of case and last time after scorpion sting.

Geriatric population:
Reduction amount of working cell disease (atrophy) holder old is more affected from scorpion
poison. For this reason antiserum treatment should be started as far as possible. Apply to dose
may be increase folded or more according to severity of case and last time after scorpion
sting.

4.3 Contra-indications
The medicine is contraindicated in patient which sensitive against immunoglobulin F(ab’)
fragments (equine) active substance or any from excipients.

4.4 Special usage warnings and precautions
Certain precautions should be taken for prevent possible anaphylactic shock which 6-10 days
after antiserum application or during usage or serum sickness.

•  Prior to the administration of the antiserum, Patient’s exposed whether to horseproteins and observed whether any allergic reactions should be researched. In patients who previously observed allergic reaction, allergic and anaphylactic reaction risk is higher.
•  ACSERA should be cautiously used in allergic cases as asthma and infantile.
•  Intradermal test is offered before ACSERA application. Inject the 0,1 – 0,2 mL (1/10 dilution) of sera by intradermal way. The doctor is decided to intradermal test whether do and application time of this test according to general medicinal condition of patient and life threat. Positive test is appeared as papilla with / without environmental erythema in 30 minutes. In cases which intradermal test is determined as positive; antihistaminic and adrenalin should be given to patient by intravenous before application of antiserum (from 0,1 % adrenalin solution; as doses 0,5 mL for adult patients and 0,01 mL/kg for children by subcutaneous or intravenous way) and antiserum should be applied at least 2 hours after keep under observation of patient. For all patients adrenalin solution should be kept ready before application of antiserum even if intradermal test is negative. If after application of antiserum; muscle pain, nausea, sudden fever and skin eruption are observed; the antiserum should be stopped immediately. If serum sickness is occur, calcium preparat is applied by intravenous way and antihistaminic should be given by oral way. After shock treatment, antihistaminic treatment should be continued during 10 days. · If tourniquet had been applied after scorpion sting, tourniquet should be loosened after given antiserum.
•  The patient should be kept under observation after application of antiserum during 30 minutes. If indications of acute hypersensitivity are developed, infusion should be stopped immediately.
•  Indications of recovery are pulse’s is turned to normal from tachycardia, sweating and heating extremist in cold moist skin cases, blood ressure is turned to normal in hypertension patients and respiration is reached to normal speed in tachypnea patients.
•  ACSERA is contains less than 1 mmol (23 mg) sodium in one dose. (Approximate between 16.70 – 18.68 mg). It is not expected any negative effect due to sodium.

4.5 Interaction with other medicaments and other forms of interaction
No data.

4.6 Pregnancy and lactation
General recommendation
Pregnancy Category: C
There is not enough data about usage ACSERA in pregnant.
Performed workings on the experimental animals are seen present reproductive toxicity.
Potential risk directed people is not know. (See 5.3)

Woman have been child fecundity / contraception
There is not enough data about usage ACSERA in woman have been child fecundity

Pregnancy Period
There is not enough data about usage ACSERA in pregnant.
Performed workings on the experimental animals are seen present reproductive toxicity.
Potential risk directed people is not know.

Lactation Period
There is not any negative effect of ACSERA on the child during lactation period.

Fertility ability
There is not known any effect of ACSERA on the fertility ability.

4.7 Effects on usage drive and machine
No data.

4.8 Undesirable effects
Frequency grouping of undesirable effects;
Very common (≥ 1/10); common (≥ 1 /100 to < 1/10); not common (≥ 1/1.000 to < 1/100);
rarely (≥ 1/10 000 to < 1/1000); very rarely (< 1/10 000), unknown (it is not estimating based
on this available data).
Developed reactions following application of animal origin all sera is possible.
In intramuscular Injection:
Common: Local reaction as pain and sensitivity in the injection site.
Rarely: hypotension, dyspnoea and urticaria with anaphylaxis
Intravenous injection

Diseases of nervous system
Common: Fever, facial flushing, headache and nausea (specially after high infusion speed), sensitivity reactions. Rarely: Hyptension, dyspnoea and urticaria with anaphylaxis

Immunity System Diseases
Common:
Serum sickness may occur 7 to 10 days following injection of animal origin serum. Symptoms are nephritis, myocarditis, neuritis, polyarthritis, and uveitis.

4.9 Overdose and treatment
There is not data about overdose treatment.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic Properties
ATC code: J06AA
Mechanism of action:
Venom characteristic is mainly neurotoxic, but usually contains cardiotoxic and often also myotoxic factors. The onset of clinical symptoms is rapid (within 5–30 min) following the sting. The clinical features of scorpion envenoming are vomiting, intense pain at sting site, hyperthermia, arterial hypertension, cardiac arrhythmia (sinus bradycardia or sinus tachycardia), complete atrioventricular block, sinus arrest, heart failure, ventricular ectopic beats, rarely and pulmonary oedema. Cause of death is generally respiratory failure and cardiovascular manifestations. Scorpion venom is a secretion which composed as a complex mixture of water, salts, small molecules, peptides, and proteins. Scorpions secrete a small quantity of transparent venom when initially stimulated that we propose to name prevenom. If secretion continues, cloudy and dense venom that is white in color is subsequently released. It is possible to observe
prevenom/venom mixture during the milking process, during which the clear and cloudy portions mix slowly. The prevenom contains a combination of high K+ salt and several peptides including some that block rectifying K+ channels and elicit significant pain and toxicity because of a massive local depolarization. The presence of high extracellular K+ in the prevenom can depolarize cells and also decrease the local electrochemical gradient making it more difficult to
reestablish the resting potential. When this positive change to the K+ equilibrium potential is combined with the blockage of rectifying K+ channels, this further delays the recovery of the resting potential, causing a prolonged effect. Peptides possess the majority of the biological activity. In the venom mixture, there are peptides that are specialized against vertebrates, invertebrates, or active against both. Members of all three groups are well characterized and include peptides that target all of the major ion channel types such as Na+, K+, Cl−, Ca2+, and ryanodine-sensitive Ca2+ channels. The devastating potency of the venom is caused by its ability to target multiple types of ion channels simultaneously, resulting in a massive and recurring depolarization that disables or
kills the prey or predator. Almost all neurotoxins in the venom are reported to be highly folded, disulfide-bridged molecules. Prevenom is active against both insects and mammals. Prevenom is more efficacious but less potent than venom. Chemical analysis of prevenom shows that it contains about sixfold less protein and sixteenfold higher concentration of K+ salt than venom. Another distinction between the prevenom and the venom is their mechanism of action. At the cellular level, prevenom is pharmacologically more efficacious than venom, because prevenom can depolarize myotubes at least twofold more efficiently than venom at equivalent high doses. On the other hand, venom continues to depolarize myotubes at low doses, whereas prevenom has no effect, indicating the higher potency of venom. Accordingly, prevenom and venom have different patterns of depolarizing activity.

5.2 Pharmacokinetic properties
General properties
Absorption and distribution of scorpion venom is very fast because scorpion venom have low
molecular weight while absorption and distribution of immunoglobulin have heavy chains is
slowly. It is distributed approximately in 5-6 minutes. It is performed peak in 30 minutes and
fast discarded from kidney.

5.3 Preclinical Safety Data
Preclinical data about antitoxin against scorpion sting (equine) is not observed for special
hazard for humans based on conventional studies of safety pharmacology, repeated dose
toxicity, genotoxicity, or carcinogenic potential.
Workings about reproductive toxicity are not enough in animal.
Preclinical safety test includes innocuity test (abnormal toxicity) in animals: mice (Swiss
white) and guinea-pigs. One person dose but not more than 1.0 ml has injected to five healthy
and 17 g to 22 g weighing mice by intraperitoneally. Animals have observed for 7 days. The
preparation passes the test if animals not show signs of ill health. If more than one animal
dies, the preparation not passes the test. If one of the animals dies or shows signs of ill health,
test should be repeated. The preparation passes the test if none of the animals in the second
group dies or shows signs of ill health in the time interval specified.
The test also is carried out on two healthy guinea-pigs weighing 250 g to 350 g. One person
dose but not more than 5.0 ml has injected to each animals by intraperitoneally way. Animals
are observed for 7 days. The preparation passes the test if animals not show signs of ill health.
If more than one animal dies, the preparation not passes the test. If one of the animals dies or
shows signs of ill health, test should be repeated. The preparation passes the test if none of the
animals in the second group dies or shows signs of ill health in the time interval specified.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Cresol
Glycine
Sodium chloride
Water for injection.
6.2 Incompatibilities
The product should not used because there is not incompatibility working test about this
product.
6.3 Shelf Life
36 months.
7
6.4 Special precautions for storage
Store between 2oC -8oC (refrigerator conditions). Avoid freezing, if you had freezed, freezed
products are not solve and use. It should be kept from sun light.
This vial is single use. Residual part after use should be discarded.
6.5 Feature and contents of container
ACSERA is submitted as package which in neutral, transparent, 5 ml in volume, glass vial of
the type I or II hydrolytic group, butyl tape an on flip off aluminum cover.
6.6 Destroy of residual material from pharmaceutical product and other special
precautions
Non used products or waste materials should be destroyed accordingly to “Regulations of
Medical waste disposal” and “Regulations Control of packing wastes”
7. LICENCE HOLDER
Vetal Sera Production ind.trade.co.ltd.
Organize Sanayi Bölgesi / ADIYAMAN/TURKEY
Phone : +90 416 227 07 53 – 54
Fax : +90 416 227 07 55
e-mail : vetalserum@vetalserum.com
8. REGISTRATION NUMBER: 1
9. FIRST REGISTRATION DATE / RENEWAL DATE
First registration date: 08/07/2011
Registration renewal date:
10. DATE OF REVISION OF THE SmPC
8