- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Adults and children aged 12 years and over:Oral. 10 ml syrup every 4 - 6 hours up to 4 times a day. Maximum daily dose: 40 ml
Children under 12 years:This product is contraindicated in children under the age of 12 years (see section 4.3).The elderly:Normal adult dosage is appropriate, [See Pharmacokinetics in the elderly].
Hepatic dysfunction:Experience with the use of the product suggests normal adult dosage is appropriate, although it may be prudent to exercise caution in the presence of severe hepatic impairment, [See Pharmacokinetics in the elderly].
Renal dysfunction:Caution should be exercised when administering this product to patients with moderate to severe renal impairment, particularly if accompanied by cardiovascular disease, [See Pharmacokinetics in Renal Impairment].Do not exceed the stated dose.Keep out of the reach and sight of children.
Symptoms and signsThe effects of acute toxicity from this product may include drowsiness, irritability, restlessness, tremor, palpitations, convulsions, hypertension, difficulty with micturition, gastro-intestinal discomfort, nausea and vomiting.
TreatmentNecessary measures should be taken to maintain and support respiration and control convulsions. Gastric lavage may be undertaken if indicated. Catheterisation of the bladder may be necessary. Acid diuresis can accelerate the elimination of pseudoephedrine, although the potential therapeutic gain of this procedure is now in dispute. The value of dialysis in overdose is not known, although four hours of haemodialysis removed approximately 20 % of the total body load of pseudoephedrine in a combination product containing 60 mg pseudoephedrine and 8 mg acrivastine.
PseudoephedrinePseudoephedrine is well absorbed from the gut following oral administration. After the administration of one 60 mg pseudoephedrine tablet to healthy adult volunteers, the Cmax for pseudoephedrine was approximately 180 ng/ml with tmax occurring at approximately 1.5 - 2.0 hours.
GuaifenesinGuaifenesin is well absorbed from the gastro-intestinal tract following oral administration, although limited information is available on its pharmacokinetics. After the administration of 600 mg guaifenesin to healthy adult volunteers, the Cmax was approximately 1.4 micrograms/ml, with tmax occurring approximately 15 minutes after drug administration.
DistributionThe apparent volume of distribution of pseudoephedrine (Vd/F) was approximately 2.8 l/kg. No information is available on the distribution of guaifenesin in humans.
Metabolism and elimination
PseudoephedrineThe t½ was approximately 5.5 hours. Pseudoephedrine is partly metabolised in the liver by N-demethylation to norpseudoephedrine, an active metabolite. Pseudoephedrine and its metabolite are excreted in the urine; 55 % to 90 % of a dose is excreted unchanged. The apparent total body clearance of pseudoephedrine ( Cl/F ) was approximately 6 - 6.5 ml/min/kg. The rate of urinary elimination is accelerated when the urine is acidified. Conversely, as the urine pH increases, the rate of urinary elimination is slowed.
GuaifenesinGuaifenesin appears to undergo both oxidation and demethylation. Following an oral dose of 600 mg guaifenesin to 3 healthy male volunteers, the t½ was approximately 1 hour and the drug was not detectable in the blood after approximately 8 hours.
Pharmacokinetics in Renal ImpairmentFollowing the administration of a pseudoephedrine-containing product (8 mg acrivastine + 60 mg pseudoephedrine) to patients with varying degrees of renal impairment, the Cmax for pseudoephedrine increased approximately 1.5 fold in patients with moderate to severe renal impairment when compared to the Cmax in healthy volunteers. The tmax was not affected by renal impairment. The t½ increased 3 to 12 fold in patients with mild to severe renal impairment respectively, when compared to the t½ in healthy volunteers.There have been no specific studies of this product, or guaifenesin in renally impaired patients.
Pharmacokinetics in Hepatic ImpairmentThere have been no specific studies of this product, guaifenesin or pseudoephedrine in hepatic impairment.
Pharmacokinetics in the ElderlyAfter the administration of a pseudoephedrine-containing product ( 8 mg acrivastine + 60 mg pseudoephedrine ) to elderly volunteers, the t½ for pseudoephedrine was 1.4 fold that seen in younger healthy volunteers. The apparent Cl/F was 0.8 fold that seen in younger healthy volunteers, and the Vd/F was essentially unchanged.There have been no specific studies of this product, pseudoephedrine or guaifenesin in the elderly.
McNeil Products Ltd
Foundation Park, Roxborough Way, Maidenhead, Berks, SL6 3UG