TAZOMIST DUO

Indications

• Maintenance treatment of chronic obstructive pulmonary disease (COPD)
• Reversible airways obstruction in asthma
• Rhinorrhea associated with allergic and non-allergic rhinitis

Dosage

Children: For inhalation: Child 1 month

Adults: For inhalation: 20–40 micrograms 3–4 times a day. For intranasal administration: Apply 2–3 drops 2–3 times a day into each nostril.

Mechanism of action

Ipratropium bromide acts as a competitive antagonist of acetylcholine at muscarinic receptors. This inhibition prevents bronchoconstriction and promotes bronchodilation, thereby easing airflow in obstructive airway diseases. It primarily affects M1 and M3 muscarinic receptors in the airway smooth muscle and secretory glands, reducing mucus secretion and aiding ventilation.

Pharmacodynamics

The onset of action for ipratropium bromide typically occurs within 30 to 60 minutes after inhalation, with peak effects observed at this time. Its bronchodilatory effects can last for approximately 3 to 6 hours, making it suitable for multiple doses throughout the day. The drug is less effective than beta-agonists in producing bronchodilation but has a complementary role in therapy, especially for patients with chronic conditions requiring long-term management.

Pharmacokinetics

Ipratropium bromide is administered via inhalation, leading to localized action in the lungs with minimal systemic absorption. The systemic bioavailability is low, resulting in a reduced incidence of systemic side effects. It undergoes hepatic metabolism, with metabolites excreted primarily in the urine. The elimination half-life varies but is generally around 2 hours, allowing for flexible dosing intervals. The maximal effect is usually achieved within an hour post-administration.

Adverse effects

• dizziness
• epistaxis
• dry mouth
• nausea

Interactions

• beta2 agonists

Precautions

• Avoid spraying near eyes
• Patients with convulsive disorders should use with caution

Pregnancy

Ipratropium bromide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult a healthcare provider for individual assessment.

Breast-feeding

Ipratropium bromide is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Inhalation aerosol: 20-40 micrograms per actuation
• Nebulised solution: 250 micrograms per dose
• Nasal spray: 20 micrograms per actuation

Indications

• Nasopharyngitis (common cold)
• Sinusitis (acute)
• Nasal congestion

Dosage

Children: For children aged 12-17 years, the recommended dosage is 2-3 drops of a 0.1% solution or 1 spray into each nostril 1-3 times a day as required, with a maximum duration of use of 7 days. Caution is advised for children under 12 years, as use is generally not recommended in younger children.

Adults: For adults, the usual dosage is 0.1% solution, administered as 1 spray into each nostril up to 3 times a day as required, with a maximum duration of use of 7 days.

Mechanism of action

Xylometazoline acts as an alpha-adrenergic agonist, stimulating alpha-1 adrenergic receptors on vascular smooth muscle, leading to vasoconstriction. This action reduces blood flow to the nasal mucosa, decreasing swelling and congestion. The onset of action is rapid, providing quick relief from nasal obstruction.

Pharmacodynamics

The pharmacodynamic effects of xylometazoline include significant vasoconstriction of nasal mucosa blood vessels, which leads to decreased nasal congestion. This effect can last for several hours, making it effective for acute conditions. However, prolonged use may lead to rebound congestion due to tolerance development.

Pharmacokinetics

Xylometazoline is administered intranasally, allowing for localized effects with minimal systemic absorption. Peak plasma concentrations are typically reached shortly after administration, although due to its local action, systemic effects are usually minimal. The metabolism and elimination pathways are not well characterized but are believed to involve hepatic metabolism and renal excretion.

Contra-indications

• Hypersensitivity to xylometazoline or any of its excipients
• Severe cardiovascular disease
• Closed-angle glaucoma
• Children under 6 years of age

Adverse effects

• Cardiovascular effects
• Headache
• Hypersensitivity reactions
• Nasal dryness
• Nausea
• Paresthesia
• Visual impairment
• Rebound congestion (rhinitis medicamentosa) with prolonged use
• Agitated psychosis, ataxia, hallucinations, and rare fatalities in infants and children under 6 years

Interactions

• Other sympathomimetics
• Vasoconstrictors

Precautions

• Use with caution in patients with diabetes mellitus
• Hypertension
• Hyperthyroidism
• Prolonged use should be avoided to prevent rebound congestion

Pregnancy

Manufacturer advises avoiding use during pregnancy due to insufficient data on safety.

Breast-feeding

Manufacturer advises caution as no information is available regarding the safety of xylometazoline during breastfeeding.

Storage

Store below 25°C. Do not freeze. Keep the container tightly closed.

Formulations

• {'name': 'Otrivine', 'type': 'Nasal spray', 'strength': '0.1%', 'volume': '15 ml'}
• {'name': 'Sudafed Sinus-Ease', 'type': 'Nasal drops', 'strength': '1 mg per 1 ml', 'volume': '10 ml'}

Indications

• Chronic obstructive pulmonary disease (COPD)
• Asthma
• Acute bronchospasm
• Bronchospasm associated with COPD

Dosage

Children: For children aged 6 to 12 years, the recommended dose is 250 micrograms via inhalation, up to three times a day. For children under 6 years, dosing should be determined by a healthcare professional, and the use of ipratropium in this age group requires careful consideration.

Adults: The usual adult dose for ipratropium is 500 micrograms via inhalation, administered up to four times a day. The maximum dose should not exceed 2000 micrograms in 24 hours.

Mechanism of action

Ipratropium works by inhibiting the action of acetylcholine on muscarinic receptors in the bronchial smooth muscle, leading to bronchodilation. It prevents bronchoconstriction and reduces mucus secretion in the airways, thus improving airflow and decreasing respiratory distress.

Pharmacodynamics

The onset of action for ipratropium is typically within 15 minutes, with a peak effect occurring around 1 to 2 hours after administration. Its effect can last for approximately 4 to 6 hours. It is more effective in patients with COPD than in those with asthma, though it can be used in both conditions. The drug is sometimes used in conjunction with beta-agonists to enhance bronchodilation.

Pharmacokinetics

Ipratropium is poorly absorbed from the gastrointestinal tract and has minimal systemic bioavailability when inhaled. It has a half-life of approximately 1.5 hours. The drug is primarily excreted unchanged in the urine. Its pharmacokinetic profile supports its use in inhaled formulations, as it provides localized effects with reduced systemic side effects.

Contra-indications

• Hypersensitivity to ipratropium or any component of the formulation
• Acute exacerbation of bronchospasm

Adverse effects

• Dry mouth
• Cough
• Headache
• Nausea
• Dizziness
• Pharyngeal irritation

Interactions

• Clozapine: Unknown (additive effect)
• Beta 2-agonists: Unknown (increases risk of glaucoma)
• Second-generation antipsychotics: Unknown (additive effect)

Precautions

• Use with caution in patients with glaucoma
• Patients with prostatic hyperplasia or bladder neck obstruction should be monitored closely
• Caution in patients with cardiovascular disorders

Pregnancy

Ipratropium is classified as category B. Limited data suggest it is not expected to cause harm to the fetus.

Breast-feeding

Ipratropium is excreted in breast milk but is not expected to harm a nursing infant. Consider benefits versus risks.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Inhalation solution
• Aerosol inhaler
• Nasal spray

Indications

• Nasal congestion due to rhinosinusitis
• Allergic rhinitis
• Non-allergic rhinitis
• Common cold-related nasal congestion

Dosage

Adults: For adults, the typical dose is 0.1% to

Mechanism of action

Xylometazoline acts primarily as an agonist at α_2B-adrenergic receptors, with additional activity at α_1A-, α_2A-, α_2C-, α_1B-, and α_1D-adrenergic receptors. This agonistic action leads to vasoconstriction of the blood vessels in the nasal mucosa, decreasing nasal resistance during breathing and enhancing airflow. The drug's vasoconstrictive properties also contribute to symptomatic relief of associated conditions, such as earache and sore throat, which may arise from mouth breathing due to nasal congestion.

Pharmacodynamics

Xylometazoline is effective in reducing nasal congestion, with a median onset of relief approximately 1.7 minutes after administration and peak relief at around 30 minutes. Its vasoconstrictive effect can lead to rebound swelling and congestion if used long-term, with potential for rhinitis medicamentosa. The drug also exhibits antioxidant properties, which may protect against oxidative stress associated with inflammation in the nasal passages.

Pharmacokinetics

Xylometazoline is rapidly absorbed when administered nasally, although specific pharmacokinetic parameters such as half-life and bioavailability are not well-documented. Its effects are relatively short-lived, necessitating careful management of dosing to avoid rebound congestion. Regular use past the recommended duration can lead to diminished efficacy and increased risk of adverse effects.

Adverse effects

• Rebound congestion
• Nasal mucosa irritation
• Dryness of the nasal mucosa
• Headache
• Nausea

Interactions

• volatile halogenated anesthetics + xylometazoline: Unknown (additive effect)

Precautions

• Use with caution in patients with cardiovascular disease
• Use with caution in patients with hypertension
• Use with caution in patients with hyperthyroidism
• Avoid prolonged use to prevent rebound congestion

Pregnancy

Use during pregnancy only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

Use with caution, as it is not known whether xylometazoline is excreted in human milk.

Storage

Store below 30°C. Protect from light.

Formulations

• Nasal spray
• Nasal drops

Mechanism of action

Nasal congestion is caused by various etiologies, such as rhinosinusitis and allergic or non-allergic rhinitis, leading to congestion of the venous sinusoids lining the nasal mucosa. Activation of α-adrenergic receptors leads to vasoconstriction of the blood vessels of the nasal mucosa and resumption of nasal airflow. As the most abundantly expressed in the human nasal mucosa, α_1A- and α_2B-adrenoceptors may play the most important role in vasoconstriction of the human nasal mucosa. Xylometazoline is a more selective agonist at α_2B-adrenoceptors, with affinity at α_1A-, α_2A-, α_2C-, α_1B-, and α_1D-adrenoceptors. Xylometazoline decreases nasal resistance during inspiration and expiration and increases the volume of nasal airflow. Compared to [oxymetazoline], another imidazoline nasal decongestant, xylometazoline had a slightly faster onset of action although they had a similar duration of action. In one study, subjects with nasal congestion reported relief of earache and sore throat in addition to nasal decongestion: it is speculated that oxymetazoline mediates this effect by causing vasoconstriction of the nasal mucosa that contains the venous sinuses and nasal decongestion allows breathing through the nose, providing relief from sore throat caused by mouth breathing that dries and irritates the throat.

Pharmacodynamics

Xylometazoline is a sympathomimetic agent that causes vasoconstriction of the nasal mucosa. In one study comprising subjects with nasal congestion associated with the common cold, the median time of onset of subjective relief of nasal congestion was about 1.7 minutes and the time of subjective peak relief of nasal congestion was 30 minutes. Previous studies reported rebound swelling, rebound nasal congestion, rhinitis medicamentosa, and shorter duration of decongestant effect from the long-term use of xylometazoline in healthy volunteers, suggesting that the drug is most effective if used temporarily. An early _in vitro_ study demonstrated xylometazoline to exert anti-oxidant actions, where it inhibited microsomal lipid peroxidation and mediated hydroxyl radical scavenging activity. This suggests that xylometazoline has a beneficial effect against oxidants, which play a role in tissue damage in inflammation.