Noscapine
Non opioid antitussive derived from the poppy plant
Noscapine is a phthalide isoquinoline alkaloid obtained from the poppy plant Papaver somniferum. Unlike the classical opium alkaloids morphine, codeine and thebaine, noscapine has no analgesic, sedative or addictive effects. The substance has been used for decades as a cough suppressant. In Germany, noscapine is available in Capval coated tablets and as a syrup; prescription is required.
Compared with the widely available alternatives dextromethorphan and codeine, noscapine occupies a niche: it is non opioid, does not sedate and carries no potential for dependence. For dry, agonising irritant cough without mucus production, the substance is an option in children from 6 years of age and in adults. In many countries, however, noscapine is either not available or only available to a limited extent, since modern studies and broader efficacy data are limited.
Mechanism of Action
Noscapine acts centrally to suppress cough by modulating the cough centre in the medulla oblongata. The exact molecular mechanism is less clearly defined than for opioid based antitussives. Investigations point to an interaction with σ receptors, to antagonistic effects at bradykinin receptors and to modulation of 5 HT1A serotonin receptors. This pleiotropic action leads to a reduction in cough frequency and cough intensity without any sedative or respiratory depressant effect.
Unlike morphine and codeine, noscapine does not bind to µ, κ or δ opioid receptors. As a result, the typical opioid effects of respiratory depression, constipation, miosis and dependence development are absent. The substance also has a minor histamine releasing component and a spasmolytic effect on smooth muscle, which makes it useful in irritant cough.
After oral intake, noscapine is rapidly absorbed; maximum plasma concentrations are reached after 1 to 2 hours. The half life is about 4 to 5 hours. Metabolism is hepatic via CYP2C9 and CYP3A4, with the metabolites eliminated predominantly by the kidneys. In recent years, antiproliferative effects of noscapine have also been described and are being studied in preclinical settings, though no oncological approval exists.
Indications
- Dry irritant cough without mucus production in acute respiratory infections
- Night time cough to improve sleep
- Irritant cough in asthma as an adjunct to bronchodilator baseline therapy
- Post tussive complaints after viral infections (post infectious cough)
- Irritant cough in chronic pulmonary disease without productive component
In productive cough with viscous mucus, noscapine is not indicated because cough suppression would impair expectoration. Expectorants such as ambroxol, acetylcysteine or erdosteine are the appropriate agents in that case.
Dosage and Administration
Adults and adolescents aged 12 and over: 25 to 50 mg noscapine three times daily, maximum 150 mg per day. Children 6 to 12 years: 12.5 to 25 mg three times daily, usually as syrup. Children 2 to 6 years: only on individual medical prescription, lowest effective dose. Noscapine should not be used below the age of 2.
It can be taken with or without food. The duration of therapy should be limited to the necessary minimum, typically 5 to 7 days for irritant cough in the context of a common cold. If cough persists for more than 3 weeks, medical evaluation should be sought, because chronic cough can hide more serious conditions (asthma, COPD, reflux, heart failure, malignancy).
Renal impairment: no adjustment in mild to moderate impairment; cautious dosing in severe impairment. Hepatic impairment: dose reduction in severe impairment because of slower metabolism. Older patients: lower starting dose because of possible slower elimination.
Side Effects
Uncommon and rare: nausea, drowsiness, headache, dizziness, mild constipation, dry mouth, allergic skin reactions, transient sleep disturbances.
Very rare: bronchospasm in asthmatics due to histamine release, anaphylactoid reactions, elevated liver enzymes, seizures in overdose, paraesthesia.
Important: according to current data, noscapine has no dependence potential and no tolerance development has been described. In children, some case series have reported mild behavioural changes, restlessness or sleep disturbances, which are reversible after discontinuation.
Interactions
- Coumarins (warfarin, phenprocoumon): noscapine can raise the INR; close monitoring with concomitant use
- Centrally depressant substances (benzodiazepines, opioids, alcohol): additive sedation theoretically possible, usually mild clinically
- Expectorants (ambroxol, acetylcysteine): pharmacodynamically opposite, combination not sensible
- CYP2C9 and CYP3A4 inhibitors (fluconazole, ketoconazole, amiodarone): elevated plasma levels possible, clinical relevance low
- First generation antihistamines: additive sedative effects possible
Special Notes
Contraindications: known hypersensitivity to noscapine or any excipient, productive cough with copious mucus, severe respiratory disease with risk of mucus retention, children below 2 years, first trimester of pregnancy (relative contraindication), severe hepatic impairment.
Workup of cough: cough is a symptom, not a diagnosis. Before symptomatic therapy the underlying cause should be clarified. Acute cough up to 3 weeks is most often viral, for which observation and symptomatic therapy usually suffice. Subacute cough of 3 to 8 weeks or chronic cough over 8 weeks requires workup, since conditions such as pertussis, lung cancer, reflux disease, post nasal drip or asthma may be responsible.
Pregnancy: cautious use in the first trimester, data are limited. In later trimesters use is possible with careful risk benefit evaluation. Breastfeeding: transfer into breast milk is possible; short term intake is probably unproblematic, with longer therapy the decision to breastfeed should be made case by case.
Driving ability: noscapine can cause dizziness or mild drowsiness in isolated cases. Driving ability is usually not significantly impaired, but individual reactions should be checked, especially at the start of therapy and in combination with alcohol or other centrally depressant substances.
Monitoring: clinical follow up; if response is inadequate after 5 to 7 days, therapy should be changed. In older patients or under concomitant coumarin therapy, an INR check should be considered.
You might also be interested in
- Codeine, opioid antitussive
- Dextromethorphan, non opioid cough suppressant
- Ambroxol, secretolytic for productive cough
- Acetylcysteine, mucolytic
- Erdosteine, mucolytic in COPD
Frequently Asked Questions
Is noscapine addictive?
No. Although noscapine is derived from the poppy plant, it is not an opioid and does not bind to opioid receptors. There is no known evidence of dependence, tolerance or withdrawal. The substance is therefore also not subject to the Narcotics Act.
Why not in productive cough?
In productive cough with viscous mucus, expectoration is important to clear the airways. A cough suppressant would retain secretions in the bronchial system and promote bacterial colonisation. In productive cough, mucolytics such as ambroxol or acetylcysteine are more appropriate.
When should I see a doctor?
Seek medical evaluation promptly for cough lasting more than 3 weeks, bloody expectoration, high fever, significant weight loss, night sweats, shortness of breath or marked fatigue. Cough that does not improve after 7 days of symptomatic therapy should also be investigated, because the underlying cause requires targeted treatment.
Is noscapine suitable for children?
From the age of 6 in age appropriate dosing as syrup; between 2 and 6 years only after medical consultation. Noscapine should not be used below the age of 2. In contrast to codeine and other opioids, there is no risk of respiratory depression and the safety margin is more favourable.
Sources
- EMA, European Medicines Agency
- AWMF, S3 Guideline on Acute Cough
- Gelbe Liste, Noscapine active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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