Nebzmart Gf Combipack Packet

Uses

Arformoterol tartrate is a salt of Arformoterol, the (R,R)-enantiomer of formoterol. Arformoterol is a selective beta 2-adrenergic bronchodilator. It has two-fold greater potency than racemic formoterol which contains both the (S,S) and (R,R)-enantiomers. The (S,S)-enantiomer is about 1,000-fold less potent as a beta2-agonist than the (R,R)-enantiomer. In vitro tests show that arformoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung.

Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).

Nebzmart Gf Combipack Packet is also used to associated treatment for these conditions: Asthma, Chronic Obstructive Pulmonary Disease (COPD)Airway Obstruction, Chronic Obstructive Pulmonary Disease (COPD), Increased upper airway secretion, Peptic Ulcer, Primary Axillary Hyperhidrosis, Sialorrhea (Excessive Drooling), Cardiac vagal inhibitory reflexes, Cardiac vagal inhibitory reflexes caused by General Surgery, Cardiac vagal inhibitory reflexes caused by Medication, Gastric secretions, Peripheral muscarinic effects

How Nebzmart Gf Combipack Packet works

While it is recognized that β2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and β1-receptors are the predominant receptors in the heart, data indicate that there are also β2-receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective β2-agonists may have cardiac effects. The pharmacologic effects of β2-adrenoceptor agonist drugs, including arformoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3′,5′-adenosine monophosphate (cyclic AMP). Increased intracellular cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of proinflammatory mediators from cells, especially from mast cells. In vitro tests show that arformoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Arformoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-response.

Glycopyrronium is a muscarinic antagonist with the highest affinity for M1 receptors, followed by M3, M2/M4, and M5.

Muscarinic receptors M1 to M4 are found in the lung, although M3 is predominantly responsible for bronchoconstriction and airway secretions. Secretions from salivary and sweat glands, as well as gastric acid secretions, are also predominantly mediated by the M3 receptor. Salivary and gastric acid secretions are also partially mediated by the M1 receptor. Antagonism of these receptors decreases the volume of their respective secretions, and in the case of the gastrointestinal system, reduces the acidity of the stomach.

In the cardiovascular system, muscarinic receptors M1 to M5 are all present, however the function of M5 has not been described in literature. Under normal circumstances, stimulation of the vagal nerve lowers the heart rate, potentially leading to intraoperative bradycardia. Studies in mice suggest that this stimulation is predominantly mediated by the M3 receptor, and mutant knockout mice are not susceptible to these effects.

Dosage

Nebzmart Gf Combipack Packet dosage

The recommended dose of Arformoterol nebuliser solution is one 15 mcg unit-dose ampoule administered twice daily (morning and evening) by nebulization. A total daily dose of greater than 30 mcg (15 mcg twice daily) is not recommended.Pediatric Use: COPD does not occur in children. The safety and efficacy of Arformoterol nebuliser solution in pediatric patients have not been established

The recommended dosage of Glycopyrronium is the inhalation of the contents of one capsule once daily with the ConviHaler device at the same time of day.

Side Effects

Most common adverse reactions are pain, chest pain, back pain, diarrhea, sinusitis, leg cramps, dyspnea, rash, flu syndrome, peripheral edema and lung disorder. Arformoterol can cause serious side effects, including: People with asthma, who take LABA medicines, have an increased risk of death from asthma problems. Patient should get emergency medical care if:• Breathing problems worsen quickly• After the use of rescue inhaler medicine, it does not relieve breathing problems

Inhaled medicines may cause inhalation-induced bronchospasm, dehydration, dry mouth, constipation, dizziness, insomnia, skin and subcutaneous tissue disorders, immune system disorders.

Toxicity

A death was reported in dogs after a single oral dose of 5 mg/kg (approximately 4500 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose.

Patients presenting with an overdose typically present with flushing, hyperthermia, tachycardia, ileus, urinary retention, loss of ocular accommodation, light sensitivity, mydriasis, nausea, vomiting, dizziness, light headedness, and obstipation. Patients should be treated with symptomatic and supportive therapy, which may include the use of catheters for urinary retention, cardiovascular support, airway maintenance, ventilation, or neostigmine.

The oral LD₅₀ in mice is 570 mg/kg, and in rats is 709 mg/kg. The intraperitoneal LD₅₀ in mice is 90 mg/kg, and in rats is 196 mg/kg.

Precaution

Arformoterol nebuliser should not be initiated in acutely deteriorating patients. It should be used with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, or with sensitivity to sympathomimetic drugs. Life-threatening paradoxical bronchospasm can occur.

Glycopyrronium, as a once-daily maintenance bronchodilator, should not be used for the initial treatment of acute episodes of bronchospasm, i.e. rescue therapy. Immediate hypersensitivity reactions may occur after administration of Glycopyrronium inhalation powder. As with other anticholinergic drugs, Glycopyrronium should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction.

Interaction

Although no formal drug interaction studies have been performed, Glycopyrronium inhalation powder has been used concomitantly with other drugs, commonly used in the treatment of COPD, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids without clinical evidence of drug interactions.

Volume of Distribution

The mean volume of distribution in patients aged 1-14 years old is 1.3-1.8 L/kg, with a range of 0.7-3.9 L/kg. The volume of distribution in adults aged 60-75 years is 0.42 ± 0.22 L/kg.

Elimination Route

In adults, a 66 mg topical dose of glycopyrronium reaches a C_max of 0.08 ± 0.04 ng/mL, with a T_max of 1 hour, and an AUC_0-24 of 0.88 ± 0.57 h*ng/mL.

Inhaled glycopyrronium is approximately 40% bioavailable. A 25 µg inhaled solution reaches a C_max of 34.5 pg/mL, with a T_max of 0-inf of 255 h*pg/mL.

An 8 µg/kg intramuscular dose reaches a C_max of 3.47 ± 1.48 µg/L, with a T_max of 27.48 ± 6.12 minutes, and an AUC of 6.64 ± 2.33 h*g/L.

Oral glycopyrronium has highly variable pharmacokinetics, reaching a mean C_max of 0.318 ng/mL, a T_max of 3.1 hours, and an AUC_0-24 of 1.74 h*ng/mL.

Half Life

In COPD patients given 15 mcg inhaled arformoterol twice a day for 14 days, the mean terminal half-life of arformoterol was 26 hours.

The half life after inhalation is approximately 33-53 hours. The mean half life of a 6 µg/kg intravenous dose is 0.83 ± 0.27 hours. The mean half life of oral glycopyrronium is 3.0 hours.

Clearance

• renal cl=8.9 L/hr [Healthy male subjects]

A 6 µg/kg intravenous dose has a clearance of 0.54 ± 0.14 L/kg/h. An oral solution has a clearance of 5.28-38.95 L/h/kg in healthy adults and 8.07-25.65 L/h/kg in patients with cerebral palsy.

Elimination Route

After administration of a single oral dose of radiolabeled arformoterol to eight healthy male subjects, 63% of the total radioactive dose was recovered in urine and 11% in feces within 48 hours. Direct glucuronidation of arformoterol is mediated by several UGT enzymes and is the primary elimination route.

85% of an intravenous dose was recovered in the urine, with 12 >80% of the recovered dose is the unchanged parent drug. The remainder is recovered as the inactive M9 metabolite.

Pregnancy & Breastfeeding use

Pregnancy Category C. Arformoterol nebuliser solution should be used during pregnancy, only if the potential benefit justifies the potential risk to the fetus. It is not known whether arformoterol is excreted in human milk.

There is a limited amount of data from the use of Glycopyrronium in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant doses. Glycopyrronium should not be used in pregnant or nursing women unless the expected benefit outweighs any possible risk to the unborn child or the infant.

Contraindication

Hypersensitivity to the active substance or to any of the excipients.

Acute Overdose

As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose of Arformoterol nebuliser solution.

High doses of Glycopyrronium may lead to anticholinergic signs and symptoms. However, there were no systemic anticholinergic adverse effects following a single inhaled dose of up to 150 micrograms Glycopyrronium in healthy volunteers.

Storage Condition

Arformoterol nebuliser solution should be stored at 2-8°c, protected from light and excessive heat. Do not freeze. Keep out of the reach of children

Should be stored at temperature not exceeding 25ºC but do not freeze. Should be stored in cool and dry place, protected from light.

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