Date of approval.
Date of revision.
Ambroxol hydrochloride injection instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Ambroxol Hydrochloride Injection
English name: Ambroxol Hydrochloride Injection
Hanyu Pinyin: Yansuan Anxiusuo Zhusheye
Ingredients
The main ingredient of this product is Ambroxol Hydrochloride (also known as Bromocyclohexanol Hydrochloride)
Chemical name: trans-4-[(2-amino-3,5-dibromobenzyl)amino]cyclohexanol hydrochloride
Chemical structure formula.
Molecular formula: C13H18Br2N2O-HCl
Molecular weight: 414.57
Excipients: citric acid, anhydrous disodium hydrogen phosphate, sodium chloride, water for injection.
【Properties】.
This product is a colorless clear liquid.
Indications】
For acute and chronic lung diseases with abnormal sputum secretion and poor sputum excretion function. For example, the expectorant treatment of acute exacerbation of chronic bronchitis, wheezing bronchitis and bronchial asthma.
Prophylactic treatment of post-surgical pulmonary complications.
Treatment of infant respiratory distress syndrome (IRDS) in premature infants and newborns.
Specification
2ml: 15mg
Dosage and Administration
Prophylaxis.
Adults and children over 12 years of age: 1 ampoule 2-3 times daily by slow intravenous infusion.
In severe cases, it can be increased to 2 ampoules each time.
Children aged 6-12 years: 1 ampoule 2-3 times daily.
Children 2-6 years of age: 1/2 ampoule 3 times a day
Children under 2 years of age: 1/2 ampoule twice a day.
All by slow intravenous infusion.
Treatment of infant respiratory distress syndrome (IRDS).
Total daily dosing is 30 mg/kg based on the infant’s body weight, administered in 4 divided doses.
The drug should be administered by syringe pump with an intravenous injection time of at least 5 minutes.
This injection can also be mixed with saline or Ringer’s solution for intravenous drip administration. Studies have demonstrated the stability of these mixtures in the concentration range of 0.03 mg/ml to 0.34 mg/ml, and the mixtures can be stored at room temperature for 24 hours and must be used during this time.
If saline or Ringer’s solution is not available, a 5% glucose solution may also be chosen as an alternative. In this case, the resulting solution must be used immediately.
[Adverse Reactions].
The incidence of adverse reactions is defined as follows.
Very common ≥ 1/10 common ≥ 1/100, but < 1/10 occasional ≥ 1/1000, but < 1/100 rare ≥ 1/10,000, but < 1/1000 very rare < 1/10000 unknown Available data do not allow assessment of their frequency
Immune system disorders
Occasional: erythema
Rare: hypersensitivity reactions
Unknown: Rapid-onset anaphylactic reactions, including rapid-onset anaphylaxis, angioedema, and pruritus; severe acute anaphylactic reactions have been reported, and the relationship to this drug is uncertain; such patients usually also develop hypersensitivity to other substances.
Skin and mucosal tissue disorders
Rare: rash, urticaria
Unknown: severe skin reactions (including erythema multiforme, Stevens-Johnson syndrome/neutrophilic epidermal necrolysis release and acute generalized eruptive pustulosis)
Gastrointestinal disorders
Occasional: dry mouth, constipation, salivation, dry throat
Unknown: heartburn, nausea, vomiting, diarrhea, indigestion, abdominal pain
Respiratory, thoracic and mediastinal disorders
Occasional: runny nose, dyspnea (one of the symptoms of hypersensitivity reactions)
Kidney and urinary system disorders
Occasionally: difficulty in urination
Systemic diseases and local abnormalities in drug administration
Occasionally: elevated body temperature, chills, mucosal reactions
Precautions]
Warnings
Serious anaphylaxis has been reported in post-marketing safety monitoring, so this product should be used with caution in special populations and in patients with a history of allergy and hypersensitivity (e.g. bronchial asthma and other airway hyperreactivity). If an allergic reaction occurs after administration, the drug should be discontinued immediately and symptomatic treatment should be given according to the severity of the reaction. In case of anaphylaxis, give first aid immediately.
Use with caution
Use with caution in the following cases: (1) patients with impaired renal function or severe liver disease; (2) patients with gastric ulcer; (3) patients with impaired bronchial ciliary function and large amount of secretions in the respiratory tract (patients with malignant cilia syndrome, etc., may be at risk of airway obstruction by secretions); (4) patients with glaucoma.
General Precautions
(1) It is forbidden to mix this product with other drugs in the same container, and pay attention to the combination of drugs.
(2) Very few patients may experience headache, fatigue, exhaustion and heaviness in the lower limbs if the injection speed is too fast during intravenous administration.
(3) Severe skin reactions such as Stevens-Johnson syndrome and Lyell’s syndrome (toxic epidermolysis bullosa; TEN) have been reported in a very small number of cases, and the appearance of these symptoms is related to the patient’s state at the time of use. Most of the above cases were caused by the underlying disease or concomitant drug use. If a patient develops new skin or mucosal injury after administration of the drug, promptly report to a physician and discontinue the product.
(4) Not to be used in children under 2 years of age without supervision by a healthcare professional.
Effects on the ability to drive and operate machinery
There is no evidence of any effect on the ability to drive or operate machinery. No relevant studies have been conducted.
Contraindications]
Not recommended for those with known hypersensitivity to Ambroxol Hydrochloride or other formulation ingredients.
Pregnant women and nursing mothers
Fertility
Non-clinical studies have shown no direct or indirect adverse effects on fertility.
Pregnancy
Ambroxol can cross the placental barrier. Animal studies have shown no direct or indirect adverse effects in pregnancy, embryo/fetal development, labor, or postnatal development.
Extensive clinical experience after 28 weeks of gestation has shown no adverse effects on the fetus. However, common precautions regarding the use of medications during pregnancy should be followed during pregnancy. In particular, the use of this product is not recommended in early pregnancy.
Lactation
In animal studies, the drug has been found to be secreted into breast milk. Therefore, the use of this product during lactation is not recommended.
For children]
See [Dosage and Administration].
It should not be used in children under 2 years of age without the supervision of a health care provider.
For elderly use]
No special precautions.
Drug Interactions
Synergistic treatment with antibiotics (amoxicillin, cefuroxime, erythromycin, doxycycline) may increase the concentration of antibiotics in sputum and bronchial secretions.
Drug overdose
No specific overdose symptoms have been reported to date. Based on reports of accidental overdose and/or dosing errors, the observed symptoms are consistent with known adverse reactions to this product when administered at the recommended dose and may require symptomatic treatment.
Pharmacology and Toxicology
Pharmacological effects
Ambroxol hydrochloride has the property of promoting mucus elimination and dissolving secretion, which can promote the elimination of mucus secretion and reduce mucus retention in the respiratory tract, thus promoting sputum elimination and improving respiratory status.
Toxicological studies
Genotoxicity.
The results of Ames test, chromosomal aberration test and mouse micronucleus test were negative for Ambroxol hydrochloride.
Reproductive toxicity.
No embryotoxicity or teratogenicity was observed in rats given amiloride hydrochloride orally at doses up to 3000 mg/kg/day and in rabbits given at doses up to 200 mg/kg/day. No effects on fertility were seen in male and female rats at doses up to 1500 mg/kg/day.
The NOAEL for the perinatal developmental toxicity test was 50 mg/kg/day. At a dose of 500 mg/kg/day, slight toxicity to mothers and pups was observed, with delayed weight gain and reduced litter size.
Carcinogenicity.
No carcinogenicity was observed in mice given 50, 200 and 800 mg/kg/day for 105 weeks and in rats given 65, 250 and 1000 mg/kg/day for 116 weeks by adulteration.
Pharmacokinetics
Distribution
The percentage of amiloride hydrochloride bound to plasma proteins is approximately 90% in adults and 60%-70% in neonates. The drug crosses the placenta and reaches the lungs of the fetus. 410 L of large volume of distribution indicates higher concentrations in tissues than in plasma. For example, it has been shown that the concentration of the drug in lung tissue is more than 17 times higher than that in blood.
Given the high protein binding levels of amiloride, the large volume of distribution, and the slow redistribution from tissue to blood, it is unlikely that amiloride will be eliminated to any extent by dialysis or forced diuresis.
Metabolism and Elimination
Ambroxol hydrochloride is metabolized in the liver primarily by glucosinolate binding and, to a lesser extent, by catabolism to dibromo-o-aminobenzoic acid (the latter accounting for approximately 10% of the dose), with other trace metabolites formed. Studies in human liver microsomes have shown that CYP3A4 is responsible for the metabolism of amiloride hydrochloride to dibromo-o-aminobenzoic acid.
Three days after intravenous administration, 4.6% of the dose was eliminated in the prototype form and 35.6% in the bound form in the urine.
The terminal elimination half-life of amiloride hydrochloride in plasma was approximately 10 h. In neonates given repeated intravenous doses, the elimination half-life was approximately doubled, indicating reduced clearance.
In patients with severe liver disease, the clearance of ambroxol was reduced by 20 to 40 %. In patients with severe renal impairment, accumulation of amiloride metabolites such as dibromo-o-aminobenzoic acid and glucosinolates may occur.
Ambroxol crosses the placenta and blood-brain barrier and is excreted in breast milk.
Storage
Keep airtight.
Keep out of reach of children.
Packaging
Brown medium borosilicate glass ampoule, 6pcs/box.
Expiration date
18 months
Execution Standard
Approval number】
Drug marketing license holder
Company: Fuan Pharmaceutical Group Ningbo Tianheng Pharmaceutical Co.
Registered Address: No. 6, Gong San Road, Zhenhai District, Ningbo City, Zhejiang Province
Postal Code: 315201
Telephone number: 8008574669
Fax number: 0574-86696785
Website: www.teampharm.cn
【Manufacturer】
Company name: Fuan Pharmaceutical Group Ningbo Tianheng Pharmaceutical Co.
Production Address: No.6 Gong San Road, Zhenhai District, Ningbo
Postal Code: 315201
Telephone number: 8008574669
Fax number: 0574-86696785
Website: www.teampharm.cn