Gastro-intestinal discomfort, nausea and vomiting have occasionally been reported with guaifenesin particularly in large doses.

Adverse reactions to levomenthol at the low concentration present are not anticipated.

4.9 Overdose
Gastric lavage in the conscious patient and intensive supportive therapy where necessary, as with cases of overdose with antihistaminic drugs.

5. Pharmacological properties
5.1 Pharmacodynamic properties
Diphenhydramine is a potent antihistamine and antitussive with anticholinergic and sedative properties. Recent experiments have shown that the antitussive action is discrete from H1-receptor blockade and is located in the brain stem.

Guaifenesin is reported to reduce the viscosity of tenacious sputum and is used as an expectorant.

Levomenthol has mild local anaesthetic and decongestant properties.

5.2 Pharmacokinetic properties
Diphenhydramine is well absorbed in the gastro-intestinal tract. Peak serum levels are reached at between 2 - 2.5 hours after an oral dose. Duration of activity is between 4 - 8 hours. The drug is widely distributed throughout the body, including the CNS, and some 78% is bound to plasma proteins. Estimates of the volume of distribution lie in the range 3.3 - 6.8 l/kg.

Diphenhydramine experiences extensive first-pass metabolism, undergoing two successive N-Demethylations; the resultant amine is then oxidised to a carboxylic acid. Values for plasma clearance lie in the range 600 - 1300 ml/min and the terminal elimination half life lies in the range 3.4 - 9.3 hours. Little unchanged drug is excreted in the urine.

Pharmacokinetic studies in elderly subjects indicate no major differences in drug distribution or elimination compared with younger adults.

Guaifenesin is readily absorbed after oral administration. It is rapidly metabolised by oxidation to β-(2-methyoxy-phenoxy) lactic acid. About 40% of a dose is excreted as this metabolite in the urine in 3 hours.

After absorption Levomenthol is conjugated in the liver and excreted both in the urine and bile as the glucuronide.

Renal Dysfunction

The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependant on glomerular filtration rate (GFR)

Hepatic Dysfunction

After intravenous administration of 0.8 mg/kg Diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease. However, the mean plasma clearance and apparent volume of distribution were not significantly affected.

5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to those already included in other sections of the SPC.

6. Pharmaceutical particulars
6.1 List of excipients
Sodium benzoate (E211)

Sucrose

Glucose liquid

Glycerol

Citric acid monohydrate

Sodium citrate

Saccharin sodium

Ethanol 96%

Caramel (E150d)

Ponceau 4R (E124)

Concentrated raspberry essence

Natural sweetness enhancer

Carbome