Levodropropizine

Usage

• Levodropropizine is prescribed for the symptomatic treatment of dry, non-productive cough. It is effective in relieving irritating and exhausting coughs associated with various respiratory conditions like acute and chronic bronchitis.
• Pharmacological Classification: Antitussive (cough suppressant).
• Mechanism of Action: Levodropropizine acts peripherally by reducing the excitability of tracheobronchial receptors, thereby suppressing the cough reflex. It also modulates sensory neuropeptide levels in the respiratory tract. This peripheral action differentiates it from centrally acting opioid antitussives, leading to fewer sedative effects.

Alternate Names

• (-)-(S)-Dropropizine
• Brand Names: Levopront, Levotuss, Reswas, Rapitus, Levare, Dropoleb, Hactosec, Q-Resp.

How It Works

• Pharmacodynamics: Levodropropizine primarily affects the peripheral nervous system, specifically reducing the sensitivity of cough receptors in the airways. This leads to a decrease in the frequency and intensity of cough.
• Pharmacokinetics:
  • Absorption: Rapidly absorbed from the gastrointestinal tract with high bioavailability (>75%).
  • Metabolism: Limited information is available regarding hepatic metabolism.
  • Elimination: Primarily eliminated through renal excretion (approximately 35% as unchanged drug) with a half-life of 1-2 hours. Eosinophil levels and body surface area (BSA) are significant factors influencing its pharmacokinetic profile.
• Mode of Action: The drug acts on peripheral C fibers in the airways, inhibiting the cough reflex. The exact cellular/molecular mechanisms are still under investigation, but it is believed to modulate the levels of sensory neuropeptides in the respiratory tract, reducing cough stimulation. There is no evidence of receptor binding, enzyme inhibition, or neurotransmitter modulation in the central nervous system.
• Elimination Pathways: Renal excretion is the main route, with about 35% excreted unchanged in the urine.

Dosage

Standard Dosage

Adults:

• 60 mg, up to three times daily, at intervals of at least 6 hours. The maximum daily dose is 180 mg. Administer between meals.

Children:

• 2-12 years: 1 mg/kg/dose, up to three times daily, at intervals of at least 6 hours. Maximum daily dose is 3 mg/kg. Convenient dosages by weight: 10-20 kg: 3 ml (syrup) up to three times a day, 20-30 kg: 5 ml (syrup) up to three times a day.
• <2 years: Contraindicated.

Special Cases:

• Elderly Patients: Administer with caution due to potential age-related pharmacokinetic changes. Close monitoring is recommended. Dosage adjustment may be necessary.
• Patients with Renal Impairment: Use with caution in severe renal impairment (creatinine clearance <35 mL/min). Dose adjustment based on creatinine clearance is recommended.
• Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Caution is advised in mild to moderate hepatic dysfunction, and dosage adjustment may be required.
• Patients with Comorbid Conditions: Administer with caution in patients with severe heart failure, diabetes. Careful monitoring and dosage adjustments are recommended based on the specific condition.

Clinical Use Cases

Levodropropizine’s use in these specific medical settings hasn’t been clinically established and needs further investigation:

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations (e.g., status epilepticus, cardiac arrest)

Dosage Adjustments

• Dose reductions may be necessary based on renal/hepatic function, comorbid conditions, and individual patient responses.

Side Effects

Common Side Effects:

• Drowsiness, fatigue, dizziness, nausea, vomiting, diarrhea, dry mouth, abdominal pain/discomfort, heartburn, headache, numbness, and palpitations.

Rare but Serious Side Effects:

• Allergic reactions (rash, itching, swelling, severe dizziness, trouble breathing), altered consciousness, and severe cardiovascular effects.

Long-Term Effects:

• Limited data are available on the long-term effects of Levodropropizine.

Adverse Drug Reactions (ADR):

• Anaphylaxis (rare).

Contraindications

• Hypersensitivity to levodropropizine.
• Bronchorrhea (excessive mucus secretion).
• Impaired mucociliary clearance (Kartagener syndrome, ciliary dyskinesia).
• Severe hepatic impairment.
• Pregnancy and lactation.
• Children below 2 years of age.

Drug Interactions

• CNS Depressants: Concomitant use with alcohol, benzodiazepines, or other sedatives can potentiate drowsiness and dizziness.
• Other interactions need further investigation:
  • No clinically significant interactions have been reported with beta-2 agonists, methylxanthines, corticosteroids, antibiotics, mucolytics, antihistamines.
  • Use cautiously when co-administered with medications metabolized by CYP450 enzymes, as potential interactions are not fully elucidated.
  • Interactions with OTC medications, food, and lifestyle factors like grapefruit juice or smoking are not well-established.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: D. Contraindicated in pregnancy. Animal studies have shown a mild delay in weight gain and growth, and levodropropizine crosses the placental barrier.
• Breastfeeding: Contraindicated. Levodropropizine is excreted in breast milk.

Drug Profile Summary

• Mechanism of Action: Peripherally acting antitussive, decreases excitability of tracheobronchial receptors.
• Side Effects: Drowsiness, fatigue, dizziness, GI disturbances. Rarely, allergic reactions, altered consciousness.
• Contraindications: Hypersensitivity, bronchorrhea, impaired mucociliary clearance, severe hepatic impairment, pregnancy, breastfeeding, children <2 years.
• Drug Interactions: CNS depressants.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Adults: 60 mg up to three times daily. Children (2-12 years): 1mg/kg/dose up to three times daily.
• Monitoring Parameters: Respiratory function, cough frequency/severity, CNS effects (drowsiness, dizziness), any signs of allergic reactions.

Popular Combinations

• Levodropropizine + Chlorpheniramine Maleate: This combination is used to treat dry cough associated with allergic conditions. Chlorpheniramine, an antihistamine, addresses allergic symptoms like sneezing and runny nose, while levodropropizine suppresses the cough.

Precautions

• General Precautions: Screen for allergies, assess renal and hepatic function, and evaluate for underlying respiratory conditions before starting treatment. Avoid in patients with productive cough.
• Specific Populations: See section “Dosage - Special Cases.”
• Lifestyle Considerations: Avoid alcohol while taking levodropropizine. Advise patients about potential drowsiness and its impact on driving or operating machinery.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Levodropropizine?

A: Adults: 60 mg, up to three times daily at least 6 hours apart. Children (2-12 years): 1 mg/kg/dose, up to three times daily, at least 6 hours apart. Contraindicated in children under 2 years of age.

Q2: How does Levodropropizine differ from opioid antitussives like codeine?

A: Levodropropizine acts peripherally, while codeine acts centrally. This results in fewer CNS side effects, such as sedation and respiratory depression, with Levodropropizine.

Q3: Can Levodropropizine be used in patients with asthma?

A: Use with caution. Ensure the cough is not related to excessive mucus production, which Levodropropizine might exacerbate. Address the underlying cause of the cough in asthma patients.

Q4: Is Levodropropizine safe during pregnancy or breastfeeding?

A: No, Levodropropizine is contraindicated during pregnancy and breastfeeding.

Q5: What are the most common side effects of Levodropropizine?

A: Drowsiness, fatigue, dizziness, nausea, vomiting, and diarrhea are the most commonly reported side effects.

Q6: Can I take Levodropropizine with other cough and cold medications?

A: Combining Levodropropizine with other CNS depressants, including alcohol, benzodiazepines, or other sedative cough medications, should be avoided or done cautiously with careful monitoring. Consult a physician before combining.

Q7: How long can I take Levodropropizine?

A: Treatment should be limited to the duration of the cough or as directed by a physician. Generally, it should not be taken for more than seven days. If the cough persists, re-evaluate the diagnosis and treatment plan.

Q8: Can Levodropropizine be used to treat a wet cough?

A: No. Levodropropizine is specifically indicated for dry, non-productive coughs. Its use in wet or productive coughs may lead to mucus retention and potential complications.

Q9: Are there any specific monitoring parameters for patients on Levodropropizine?

A: Monitor patients for efficacy (cough reduction), side effects (drowsiness, dizziness, GI upset), and signs of allergic reactions. In patients with renal or hepatic impairment, closer monitoring of drug levels and organ function is necessary.

Q10: What should patients do if they experience side effects while taking Levodropropizine?

A: Patients should report any side effects to their physician. For mild side effects, supportive care may be sufficient. For moderate to severe or persistent side effects, discontinuation of the medication and consideration of alternative treatment options may be necessary. For severe allergic reactions, immediate medical intervention is required.