Dextromethorphan hydrobromide is: Chemical name: 3-Methoxy-17-methyl-9a, 13a, 14a -morphinan hydrobromide monohydrate Molecular formula: C18H25NO,HBr. H2O CAS number: 6700-34-1 Molecular weight: 370.3 Structural formula:
Bisolvon Dry Oral Liquid and Bisolvon Dry Pastilles are preparations for oral administration. Each 5 mL of Bisolvon Dry Oral Liquid contains dextromethorphan hydrobromide 10 mg. Other ingredients include methyl hydroxybenzoate, saccharin sodium, maltitol solution, propylene glycol, vanilla aroma 33P080, apricot aroma 653460, and purified water. Each Bisolvon Dry Pastille contains dextromethorphan hydrobromide monohydrate 10.5 mg (equivalent to dextromethorphan hydrobromide anhydrous 10 mg). Other ingredients include betadex, acacia, sodium cyclamate, saccharin sodium, quinoline yellow, citric acid anhydrous, honey flavour 8366/001, limette flavour 18635/02, menthol, maltitol solution, paraffin light liquid, beeswax white, purified water. Dextromethorphan hydrobromide is a white or almost white crystalline powder, soluble in alcohol and chloroform, sparingly soluble in water, and practically insoluble in ether.
Dextromethorphan is a non-opioid cough suppressant. It is the methylated dextrorotatory analogue of levorphanol, a codeine analogue. Dextromethorphan acts centrally on the cough centre in the medulla and nucleus tractus solaris to increase the cough threshold. It does not have classical analgesic, sedative or respiratory depressant effects at usual antitussive doses. The onset of antissive effect occurs within an hour and the duration of action is approximately 3 - 6 hours.
Absorption:
Dextromethorphan is well absorbed from the gastrointestinal tract after oral administration. Metabolism: It is metabolised in the liver, exhibiting polymorphic metabolism involving the cytochrome P450 isoenzyme (CYP 2D6).
Elimination:
It is excreted in the urine as unchanged dextromethorphan and demethylated metabolites, including dextrorphan, which has some cough suppressant activity. The plasma elimination half-life of dextromethorphan is 1.2 to 3.9 hours. However, the rate of metabolism varies between individuals according to phenotype (extensive v poor metabolisers), with half-life being as long as 45 hours in patients who are poor metabolisers.
Bisolvon Dry Oral Liquid and Bisolvon Dry Pastilles are used for the symptomatic treatment of dry, irritant, unproductive coughs. Bisolvon Dry Pastilles also helps soothe the throat.
Dextromethorphan is contraindicated for use in patients with known hypersensitivity or idiosyncratic reaction to dextromethorphan (or any other ingredients in the product - refer 'Adverse Effects' for effects of maltitol and sorbitol.) Patients with fructose intolerance should not take Bisolvon Dry Oral Liquid and Bisolvon Dry Pastilles. Refer to 'Interactions with other medicines' for additional information.
Dextromethorphan should not be used for chronic persistent cough accompanying a disease state, or for cough associated with excessive secretions. Dextromethorphan should not be given to patients with or at risk of developing respiratory failure, e.g asthma, chronic obstructive airways disease, and pneumonia. Caution is needed in patients with a history of asthma and it should not be given during an acute attack. Refer to 'Interactions with other medicines' for additional information.
Experimental studies with dextromethorphan hydrobromide and observations in humans have not shown harmful effects on reproduction or on foetal development. Because animal studies are not always predictive of human response, Bisolvon Dry Oral Liquid and Pastilles should not be used in the first three months of pregnancy; in later pregnancy periods it should only be taken if clearly needed.
Category A: Dextromethorphan has been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.
The extent of excretion in breast milk is not known; therefore, the use of Bisolvon Dry Oral Liquid and Bisolvon Dry Pastilles is contraindicated during lactation since a respiratory depressive effect on infants cannot be ruled out.
Do not use Bisolvon Dry Oral Liquid in children under 6 years of age. Do not use Bisolvon Dry Pastilles in children under 6 years of age. Use in children aged 6 - 11 years only on the advice of a doctor, pharmacist or nurse practitioner. If the cough persists for more than 1 week, a doctor should be consulted for further diagnostic clarification.
Bisolvon Dry Oral Liquid and Bisolvon Dry Pastilles should be used with caution in patients with impaired liver function or who are receiving a monoamine oxidase inhibitor antidepressant; in case of doubt, these patients should ask for medical advice.
Even when used as prescribed this medication may cause mild drowsiness and alter reaction times to the extent that the ability to drive or to operate machinery is impaired. The risk is increased when it is taken in combination with alcohol or with medications that can impair reaction times.
Dextromethorphan has addictive potential. Following prolonged use patients may develop tolerance as well as mental and physical dependence. Patients with a tendency towards abuse or dependence should only be given Bisolvon Dry(r) for short periods and under strict medical supervision.
The following interactions with dextromethorphan have been noted: Dextromethorphan should not be used in patients taking monoamine oxidase inhibitors (MAOIs) or who have taken MAOIs within the previous 14 days. The use of dextromethorphan with, or within two weeks of taking MAOIs, may increase the risk of serious side effects such as hypertensive crisis, hyperpyrexia and convulsions. Dextromethorphan when used with SSRI's (such as fluoxetine) or tricyclic antidepressants (such as clomipramine and imipramine) may result in a "serotonin syndrome" with changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering and tremor. Serum levels of dextromethorphan may be increased by the concomitant use of inhibitors of cytochrome P450 2D6, such as the antiarrhythmics quinidine and amiodarone, antidepressants such as fluoxetine and paroxetine, or other drugs which inhibit cytochrome P450 2D6 such as haloperidol, cimetidine, ritonavir and thioridazine. Concomitant use of dextromethorphan and other CNS depressants (e.g. alcohol, narcotic analgesics and tranquillizers) may increase the CNS depressant effects of these drugs. If dextromethorphan is used in combination with secretolytics the reduced cough reflex can lead to serious accumulation of mucus.
Side effects with usual doses are uncommon but may include mild drowsiness, fatigue, dystonias, dizziness and gastrointestinal disturbances (nausea or vomiting, stomach discomfort, or constipation). Side effects that may occur with high doses (overdosage) include excitation, confusion, psychosis, nervousness, irritability, restlessness, "serotonin syndrome", severe nausea and vomiting, and respiratory depression. Cases of dextromethorphan abuse and dependency have been reported (refer 'PRECAUTIONS'. Bisolvon Dry Oral Liquid contains at least 3 g of maltitol and up to 1 g of sorbitol in 10 mL and Bisolvon Dry Pastille contains at least 5.1 g of maltitol and 0.8 g of sorbitol per maximum recommended daily dose, which may have a laxative effect or cause diarrhoea in some people. This is more likely if several products containing maltitol, sorbitol or other related substances are consumed simultaneously. Patients with the rare hereditary condition of fructose intolerance should not take this medicine as it may cause severe abdominal pain, vomiting and hypoglycaemia due to presence of maltitol and sorbitol. The frequency of undesirable effects is based of the following categories: Very Common >= 1/10 Common >= 1/100 < 1/10 Uncommon >= 1/1,000 < 1/100 Rare >= 1/10,000 < 1/1,000 Very Rare < 1/10,000 Not known cannot be estimated from the data available
Psychiatric disorders, Nervous system disorders, General disorders and administration site conditions Common:dizziness, fatigue Very rare:drug dependence have been reported in individuals abusing dextromethorphan, somnolence, hallucinations
Immune system disorder Not known:hypersensitivity Gastro-intestinal disorders Common:nausea, vomiting and gastrointestinal disorder
The following dosage regimen is recommended:
Adults and children over 12 years:
5 - 15 mL of Bisolvon Dry Oral Liquid, every 4 - 6 hours when necessary. The maximum total daily dose is 60 mL of Bisolvon Dry (equivalent to 120 mg dextromethorphan hydrobromide). Do not exceed 4 doses in a 24 hour period.
Children 6 - 11 years:
2.5 - 7.5 mL of Bisolvon Dry Oral Liquid, every 4 - 6 hours when necessary. The maximum total daily dose is 30 mL of Bisolvon Dry (equivalent to 60 mg of dextromethorphan hydrobromide). Do not exceed 4 doses in a 24 hour period.
Adults and children over 12 years: Slowly suck 1 - 3 pastilles (10 - 30 mg dextromethorphan hydrobromide) every 4 - 6 hours when necessary. The maximum total daily dose is 12 pastilles (equivalent to 120 mg dextromethorphan hydrobromide).
Children 6 to 11 years:
Slowly suck 1 pastille (10 mg dextromethorphan hydrobromide) every 4 - 6 hours when necessary. The maximum total daily dose is 6 pastilles (equivalent to 60 mg of dextromethorphan hydrobromide). If the cough persists for more than 1 week, a doctor should be consulted for further diagnostic clarification.
In case of overdose, immediately contact the Poisons Information Centre (call 13 11 26) for advice.
The effects of an overdose include nausea, vomiting, vision impairment and CNS-disorders like ataxia. Dizziness, excitation, increased muscle tonus, impaired consciousness, drop in blood pressure, tachycardia, agitation and hallucinations may occur. In extreme cases, urinary retention and respiratory depression may ensue.
If necessary initiate intensive medical measures (in particular intubation, ventilation). Measures to guard against heat loss and volume replacement may also prove necessary. The intravenous administration of naloxone may antagonise the central nervous effects of dextromethorphan. Do not administer centrally acting emetics.
Bisolvon Dry Oral Liquid is a clear, colourless, syrupy liquid with an aroma of apricot and vanilla, available in amber-coloured bottles containing 200 mL. Each 5 mL contains 10 mg dextromethorphan hydrobromide. Bisolvon Dry Pastille is a yellow, round pastilles with a honey lime flavour, available in blister packs containing 10, 20, 30 and 40 pastilles. Each pastille contains 10.5 mg dextromethorphan hydrobromide monohydrate (equivalent to 7.7mg dextromethorphan or 10 mg dextromethorphan hydrobromide anhydrous). Bisolvon Dry Oral Liquid should be stored below 30oC and protected from direct sunlight. Bisolvon Dry Pastille should be stored below 25oC Not all pack sizes are distributed in Australia.
Boehringer Ingelheim Pty Limited ABN 52 000 452 308 78 Waterloo Road North Ryde NSW 2113
S2 - Pharmacy Medicine
Bisolvon Dry Oral Liquid -AUST R 68185 was first registered 19 Mar 1999 Bisolvon Dry Pastilles - AUST R 191459 was first registered 3 November 2011
Text approved by Therapeutic Goods Administration (TGA) on 25 Jan 2012