Please read the instructions carefully and

take the product  under the guidance of the pharmacists

 

Common name: Naloxone hydrochloride Injection

English name: Naloxone hydrochloride Injection

Pinyin:Yansuan Naluotong Zhusheye

Ingredients:

the main ingredient is Naloxone hydrochloride , its chemical name is:

17 - Allyl -4,5 epoxy -3,14 -dihydroxy-morphine furans -6 -hydrochloride dihydrate

Its molecular formula:
Its Molecular Weight : 399.87

Properties : This product is a colorless and transparent liquid.

Indications: This product is opioid receptor antagonist.

1.It is indicated to treat the symptom of post Opioids for post-anesthesia, antagonize such drug-induced respiratory depression and bring the patients to themselves.

2.It is used for over opioid overdose, complete or reverse opiod-induced respiratory depression.

3.It is used to treat acute alcohol poisoning.

4.It is used for the diagnosis of over opioid overdose

(1)1ml:0.4mg

(2)2ml:2mg

(3)1ml:1mg

(4)10ml:4mg

As a result of obvious individual differences for the product, it is suggested that the application should be based on the specific circustances of the patients and whether the patients should require the product by doctors.

The injection is administered by intravenous or intramuscular injection , intravenous injection pvovides a quick effect and suitable for use in emergency.

    Because the effect of opioid may exceed the duration of the injection, the patient should be in constant ward, if necessary,  the injection can be used again and again.

the injection canbe diluted by saline or glucose solution,add the injection 2mg to500ml either kind of the liquids, so that the concentration can reach 0.004mg/ml,

the mixture should be used within 24 hours, more than 24 hours, if it remains unused,then the mixture must be discarded. The speed of Drip should be under control of according to the patient^,s response .

   For overdosage of opioid, for the first time, we can use 0.4mg-2mg of the product for intvavenous injection. If we don^,t get the ideal effect for respiratory function or improvement, we can inject the product 2-3 minutes later. If 10mg of the product is injected, without any effect, then we should take the diagnosis into consideration. If we can^,t admister intravenous injection, then intramuscular injection. Usually, small dosage of the product can have satisfactory effect on the inhibitory effects of opiods.The dosage should be based on the response of patients. After inhibitory effects of opioids, some corrective surgery at the use of opioids after the inhibitory effect of opioid, usually in small doses that have the effect of the goods. The dosage should be based on the response of patients. For the first time to correct respiratory depression, we can use intravenous injection with a dosage of 0.1-0.2mg every 2-3 minutes, until we get satisfactory effect(unobstructed breathing and sober, no significant pain and discomfort), If overdosage of the injection is injected, we can significantly reverse the pain and hoist blood pressure. At the same time, if it is reversed too fast, it can cause nausea, vomiting, sweating or recycling burden. Within one or two hours, the use of the dosage depends on the final amount of opioids used and the administration type( short or long) and the interval.

For severe alcohol poisoning, inject 0.8mg-1.2mg, one hour later, another 0.4mg-0.8mg is injected again.

  For overuse of opioids, for the first time, pediatric intravenous dose should be limited to 0.1mg/kg, if the dose doesn^,t bring satisfactory clinical results, next we should inject 0.1mg/kg. If intravenous injection can^,t be used, we can try intramuscular injection for several times, if necessary, we can dilute the product with sterile water for injection.

   As to the inhibitory effects of opioids after operation, refer to the recommendations and notes given to adults, for the first time to correct respiratory depression, we can use intravenous injection with a dosage of 0.005-0.1mg every 2-3 minutes, refer to the indications given to adults and repeat the dosage until we get a satisfactory result.

  As to the inhibitory effects of opioid after operation, we can exercise intravenous, intramuscular or subcutaneous injection, usually with the initial dosage 0.01mg/kg, refer to the recommendations and notes given to adults the indications given to adults and repeat the dosage.

  To diagonise if the patient is opioid tolerant or has an opioid overdose .give an intravenous injection with the dosage of 0.2mg, then observe the patient for 30 seconds to see if there is the symptoms or signs of opiate withdrawal, if not, every time, inject 0.6mg, then observe another 20minutes..

  The product shouldn^,t be given to those with the symptom or signs of obviousopiate withdrawal, or those with opioids contained in their urine

 Some patients, especially those who are opioid tolerant will react to low dosage of the product. A dosage of 0.1mg will help by intvavenous injection.

 After operation Such synptoms can be found occassionally, low blood pressure, high blood pressure, Ventricular tachycardia and ventricular fibrillation, dyspnea, pulmonary edema and cardiac arrest, the reported after-effects have :death, coma, and encephalopathy. The excessive use of the product may reverse the loss of pain and excitement of the patients.

   A sudden reversal of opioid inhibition may lead to nausea, vomiting, sweating, palpitations hyperthyroidism, hypertension, shivering, epilepsy seizures, ventricular tachycardia and ventricular fibrillation, pulmonary edema and cardiac arrest and even death.

The suddent reversal of opioids for those opiate-dependent patients may lead to acute withdrawal syndrome, including but not limited to the following symptoms and signs: physical pain, fever, sweating, palpitations hyperthyroidism, erect hair, yawn, weakness, chills, or shaking, nervous anxiety or excitement, diarrhea, nausea or vomiting, abdominal cramps, hypertension, hyperthyroidism heart palpitations.

For newborns, the possible symptoms of opioid withdrawal may include: convulsions, excessive crying, excessive reflex activity.

the adverse reactions for the use of the product or reducing the use of the product can be classified according to organ system as follows:

pulmonary edema, cardiac arrest or failure, hyperthyroidism heart palpitations, ventricular fibrillation and ventricular tachycardia. It is reported that after-effects have caused the death, coma, and encephalopathy

Stomachs and intestines: Vomiting, nausea.

Psychiatry: Excitement, hallucinations, shake

Respiratory tract, chest and dissepiment: dyspnea, respiratory depression, hypoxia syndrome.

Skin and subcutaneous injection: Non-specific injection site reactions, sweating

Vascular disease: High blood pressure, low blood pressure, hot flashes and redness

Contradiction: Do not administer this product to those who are hypersensitive to it

1. this product should be used with caution in known or suspected opioid-dependent patients, including the newborns whose mothers are opioid-dependent, for such cases , a sudden or complete reversal of opioid may lead to acute withdrawal syndrome.

2. Because the role of some opioids is longer then that of naloxone, continous attention should be paid to those patients who enjoy good effects. If necessary, we should exercise repeat administration.

3. This product has no effect on non-opiate-induced respiratory depression and the control of left C-fen-induced acute oxygen toxicity. Only partially reverse the partial agonist or mixed agonist / antagonist( such as buprenorphine and pentazocine )caused by respiratory depression or increase the amount of naloxone, if this can^,t work, we then need to treat respiratory depression mechanically in clinical phase.

4.  After operation, A sudden reversal of opioid inhibition may lead to nausea, vomiting, sweating, palpitations hyperthyroidism, hypertension, shivering, epilepsy seizures, ventricular tachycardia and ventricular fibrillation, pulmonary edema and cardiac arrest and even death. The excessive use of the product may reverse the loss of pain and excitement of the patients.

5. If the patient has the history of cardiovascular disease, or other serious adverse cardiovascular reactions ,( hypotension, ventricular tachycardia or ventricular fibrillation, pulmonary edema), when using the drug, we should be careful.

6. After the use of high-dose Naloxone antagonism of narcotic analgesics. Because of the recovery of pain,  the patient can have a high degree of excitement. The symptoms are high blood pressure, heart rate increased quickly, arrhythmia, or pulmonary edema and ventricular fibrillation.

7. Because the drug can only help within a short period of time, after the drug works, its role disappears, the patients will get into re-drowsiness and respiratory depression, so we should pay attention to the maintenance of drug efficacy .

8. if the patients have liver disease, renal insufficiency / failure, the safety of the use of naloxone has not yet been established, when using the drug, we should be careful.

1. The tests of reproductive toxicity carried out by the human dose, (respectively, 4-8 times )on mouse and rat show that naloxone doesn^,t have embryo-toxic or lead to deformities. Because we haven^,t carried out effective research on women in pregnancy, therefore pregnant women can only consider medication when necessary.

2. Usually if a mother is opioid-dependent, at the same time, so will her fetus. So before the known or suspected opioid-dependent pregnant women  are injected the the product, we should consider the danger to the fetus. Naloxone can induce the mother and fetus withdrawl symptoms, light to medium labor, the use of naloxone should be in close custody to avoid serious high blood pressure.

3. It is not clear whether the product will affect the labor/deliver time, however, the studies published have shown that the use of naloxone has no negetive effect on mothers or newborns.

4. It is not clear yet whether the product will be secreted through breast milk, because the product may be secreted into human milk. When breast-feeding women are injected the product, they should be careful.

1.      The product can reverse the effect of opioids on children or newborns. The children who are opioid-poisoning have s strong reflection of the product, which needs a 24-hour close care until the product is discharged.

2.      At the beginning of a mother^,s delivery,  if a mother is injected the product into, the product can only extend the newborn^,s life fow two huors. If necessary, we can directly inject the product into newborns after birth .

We don^,t have enough clinical trials for patients at the age of 65 or over 65 that are injected the product into . We haven^,t found the differences of response to the drug between the elderly patients and young patients.In general, taking into account the reduced heart function of the liver, kidney and heart and great chances of other accompanying diesases, we should exercise caution and the dosage should begin with small dosage.

1.The low binding rate of buprenorphine with the opioid receptor and its slow separation determine its long-time role. So we should inject high-dose naloxone against buprenorphine.We should gradually strengthen the antagonistic efeect of buprenorphine and shorten the time of respiratory depression.

2.Barbital acetylene may block the acute withdrawal symptoms of naloxone-induced opioid addicts.

3.Don^,t mix the product with the chemicals containing dium bisulfate, sodium bisulfite, long-chain anionic polymer or any mixture alkaline agents. Before adding drugs or chemical reagent to the product, first determine its impact on the product toward the product^,s chemcial and phycial stability

For the patients who are injected too much naloxone, we should carry out symptomatic treatment and give them intensive care.

In a small experiment, volunteers accept 24mg/70kg drug treatment, it doesn^,t show any signs of toxicosis. In another experiment, 36 cases of acute stroke patients accepted 4mg/kg(10mg/m2/min) naloxone treatment, later the dosage changed to 2mg/kg/hr, they accepted a total of 24-hour treatment. Among them, 23 had adverse reactions, 7 stopped foraverse drug reaction. The most serious adverse reactions were as follows: epileptic seizures (2 cases) severe hypertension (1 case), and low blood pressure and heart bradycardia (3 cases)

If we inject the drug 2mg/kg into healthy people, it is reported that there is emergence of ccognitive impairment and behavioral abnormalities, including prone to excitement, anxiety, stress, paranoia, sadness, lack of concentration and anorexia, in addition to physical symptoms, including reported dizziness, heart, sweating nausea and stomach pain. These persistent behavioral symptoms will last 2-3 days.

 For children who are injected too much diphenoxylate hydrochloride and atropine sulfate, we can only inject naloxone 2.2mg,  a pediatric report showed a 2-year-old baby was injected 20mg naloxone.The baby was in good health, there were no affter-effects after restore. Another report showed that a 4-year-old baby was injected 2.2 naloxone into , there is no sequelae.

The product is opioid receptor antagonist. It has almost no pharmacological activity itself. But it can it is an antagonist against all types of opioid receptors, it has a strong affinity to u receptor.

1. It can correct the central opioid inhibitory effects wholy or partially, such as respiratory depression , sedation and hypotension.

2. It is helpful to wakinging up animals of acute ethanol poisoning of.

3.As an opioid receptor antagonist, it has none of the effects of opioid receptor antaonist( such as: excitement or morphine effect). It doesn^,t cause respiratory depression, mental illness and hitomi reduction reaction.

4. For the opioid receptor antagonist, neither of the other opioid receptor antagonist "excited" or morphine effect, not cause respiratory depression, mental illness to be reduced pupil response or reaction.

5. it doesn^,t show any signs of resistance ,physical or psychic dependence.

6. although its mechanism is not entairely clear. There is sufficient evidence to show it is working by it is fighting for the same point against opioid recetors.

In the clinical research of the Institute of Chinese Neurosurgery and Neurosurgey Journal of China, 18 major hospitals nationwide( including the nerve specialist hospitals) did a double-blind, randomized and controlled clinical study of its treatment of acute head injury. In  the finished 500cases, the expeimental group used the product besides the basic treament. With a dosage of 0.3mg/kg,body/day and normal saline or diluted fluid 500ml. it is infused continuously 24 hourswith infusion pumps. Three days later, the dosage is reduced to 4.8ma/day, for another consecutive seven days, , we compared the results of pilot group (basic treatment without the product) with those of the experimental group. It shows the death rate of the experimental group is 12.5% ,while the pilot group is 17.3% . there were clear differences. The scores of its GCS and GOS, language exercise function and quality of life were significantly better than the pilot group. During the treatment, a total of 8 cases showed the signs of varying degrees of liver and kidney dysfunction. But no evidence showed it was connected with the drug.

1.If we give single dose intravenous injection, the LD₅₀s of rats and mice are 150mg/kg and 109mg/kg separately. For a single dose subcutaneous injection , neonatal rat LD50 is 260mg/kg.

2. We haven^,t carried out the animal experiments to evaluate if it contains carcinogenic chemicals.

3. We give mice and rats 50 times the amount of that of people to test is effect on fertility, the result shows there is no damage to the role of fertility.

When the product is injected intravenously, the product will usually take effect within two minutes. It usually takes a long time for the intramuscular or subcuttaneous injection to do its work. And the length of time that it sustains usually depends on the dosage and the means of delivery. The time of intramuscular injection that it sustains is usually longer than that of tntravenous injection. However ,  whether the product is injected again and again depends on the dosage of the opioid antagonist , its type and means.

When the product is not administered intestinally, the product distributes quickly through the placenta.it has little chance for the product to bind with plasma protein. Naloxone mainly binds with plasma albumin.. it can also with the other components of plasma.  It is not clear whether naloxone is excreted through human milk.

The product is metabolized in the liver. It mainly combine with glucuronide,  the main metabolite is naloxone -3 - glucuronic acid compound. In a research, the erum half-life of the drug in vivo is 30-81 minutes( on average 52-76 minutes), when it is orally or intravenously, about 25-40% of the product is metabolized, whithin 6 hours, it is discharged through urination.within 24 hours, 50% is discharged, within 72 hours, 60-70 is discharged.

Kept in the dark and cold place.( not more than )

Validity: 24 months

Executive Standard: State Food and Drug Administration standard  YBH15162006

(1). 1ml:0.4mg  SFDA approval number20065378  

(2). 1ml:1mg    SFDA approval number H20065376

(3) .2ml: 2 mg   SFDA approval number H20065377  

(4). 10ml:4mg   SFDA approval number H20065379

Hebei Aoxing Pharmaceutical Group Co,Ltd.

Address: No.1,Nanhuan donglu XinLe city, Hebei province.

Zip Code: 050700

Tel: 0311-85196666

Fax : 0311-851964444