Summary of Product Characteristics (SmPC) - Lactulose 3.335 g/5 ml oral solution
1 NAME OF THE MEDICINAL PRODUCT
Lactulose 3.335 g/5 ml Oral Solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Lactulose 3.335 g/ 5 ml Oral Solution (as Lactulose, liquid 667 g/L)
For a full list of excipients, see 6.1
Lactulose 3.335 g/5 ml Oral Solution contains residues from the route of production with known effect, see section 4.4
3 PHARMACEUTICAL FORM
Oral solution.
A clear, viscous liquid, colourless to pale-brownish yellow.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
- 1. For the treatment of constipation.
- 2. For the treatment of hepatic encephalopathy (HE); hepatic coma.
4.2 Posology and method of administration
Posology
The lactulose solution may be administered diluted or undiluted. Each dose may if necessary be taken with water or fruit juices, etc.
Each dose of lactulose should be swallowed in one and should not be kept in the mouth for an extended period of time.
The posology should be adjusted according to the individual needs of the patient.
In case of single daily dose, this should be taken at the same time, e.g. during breakfast.
During the therapy with laxatives it is recommended to drink sufficient amounts of fluids (1.5–2 litres, equal to 6-8 glasses) during the day.
Dosing in constipation:
Lactulose may be given as a single daily dose or in two divided doses. After a few days the starting dosage may be adjusted to the maintenance dose based upon treatment response. Several days (2-3 days) of treatment may be needed before treatment effect occurs.
Lactulose 3.335 g/5 ml Oral Solution in bottles:
| Starting dose daily | Maintenance dose daily | |
| Adults and adolescents | 15-45 ml | 15-30 ml |
| Children (7-14 years) | 15 ml | 10-15 ml |
| Children (1-6 years) | 5-10 ml | 5-10 ml |
| Infants under 1 year | up to 5 ml | up to 5 ml |
Dosing in Hepatic Encephalopathy
Adults
Starting dose: 3 to 4 times daily 30-45 ml
This dose may be adjusted to the maintenance dose to achieve two or three soft stools each day.
Method of Administration
Oral use
For lactulose in bottles the measuring cup may be used.
Special populations
Paediatric population
The safety and efficacy in children (newborn to 18 years of age) with HE have not been established. No data are available.
Elderly patients and patients with renal or hepatic insufficiency
No special dosage recommendations exist, since systemic exposure to lactulose is negligible.
4.3 Contraindications
Hypersensitivity to the active substance or any of the excipients listed in section 6.1.
Galactosaemia.
Gastro-intestinal obstruction, digestive-perforation or risk of digestive perforation.
4.4 Special warnings and precautions for use
Painful abdominal symptoms of undetermined cause should be evaluated to exclude undiagnosed perforation or obstruction or undiagnosed disease/condition that predisposes to either before the treatment is started.
In case of insufficient therapeutic effect after several days the dose and/or additional measures should be re-considered.
Chronic use of unadjusted doses and misuse can lead to diarrhoea and disturbance of the electrolyte balance.
It should be taken into account that the defaecation reflex could be disturbed during the treatment.
The dose normally used in constipation should not pose a problem for diabetics.
The dose used in the treatment of HE is usually much higher and may need to be taken into consideration for diabetics.
Information on residues from manufacturing with known effect:
This product contains lactose, galactose and fructose from the route of production. Therefore, patients with rare hereditary problems of galactose or fructose intolerance, the total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Lactulose should be administered with care to patients who are intolerant to lactose.
This product contains sulphite from the route of production.
Paediatric population
Use of laxatives in children should be exceptional and under medical supervision.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
4.6 Fertility, pregnancy and lactation
Pregnancy
No effects during pregnancy are anticipated, since systemic exposure to lactulose is negligible.
Lactulose can be used during pregnancy.
Breast-feeding
No effects on the breastfed newborn/infant are anticipated since the systemic exposure of the breast-feeding woman to lactulose is negligible.
Lactulose can be used during breast-feeding.
Fertility
No effects are to be expected, since systemic exposure to lactulose is negligible.
4.7 Effects on ability to drive and use machines
Lactulose 3.335 g/5 ml Oral Solution has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Flatulence may occur during the first few days of treatment. As a rule it disappears after a couple of days. When dosages higher than instructed are used, abdominal pain and diarrhoea may occur. In such a case the dosage should be decreased. See also overdose section 4.9.
If high doses (normally only associated with hepatic encephalopathy, HE) are used for an extended period of time, the patient may experience an electrolyte imbalance due to diarrhoea. Dosage should then be adjusted to obtain two or three formed stools per day.
Tabulated list of adverse reactions
The following undesirable effects have been experienced with the below indicated frequencies in lactulose-treated patients in placebo-controlled clinical trials:
very common (≥1/10);
common (≥1/100 to <1/10);
uncommon (≥1/1,000 to <1/100);
rare (≥1/10,000 to <1/1,000);
very rare (<1/10,000)
not known (frequency cannot be estimated from the available data)
| MedDRA SOC | Frequency category | |||
Very common | Common | Uncommo n | Not known | |
| Gastrointestin al disorders | Diarrhoe a | Flatulenc e, abdomina l pain, nausea, vomiting | ||
| Investigations | Electrolyte imbalance due to diarrhoea | |||
| Immune system disorders | Hypersensitivit y reactions | |||
Skin and subcutaneous tissue disorders | Rash*, puritis*, urticaria* | |||
*Post-marketing experience
Paediatric population
The safety profile in children is expected to be similar as in adults.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
If the dose is too high, the following may occur:
Symptom: diarrhoea, loss of electrolytes and abdominal pain.
Treatment: cessation of treatment or dose reduction. Extensive fluid loss by diarrhoea or vomiting may require correction of electrolyte disturbances.
No specific antidote. Symptomatic treatment should be given.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Osmotically acting laxatives, ATC code: A 06A D11
In the colon, lactulose is broken down by colonic bacteria into low molecular organic acids. These acids lead to a lowering of pH in the colonic lumen and via an osmotic effect to an increase of the volume of colonic contents. These effects stimulate peristalsis of the colon and return the consistency of the stool. The constipation is cleared and the physiological rhythm of the colon is reinstated.
In hepatic encephalopathy (HE), the effect has been attributed to suppression of proteolytic bacteria by an increase of acidophilic bacteria (e.g. lactobacillus), trapping of ammonia in the ionic form by acidification of the colonic contents, catharsis due to the low pH in the colon as well as an osmotic effect, and alteration of the bacterial nitrogen metabolism by stimulating the bacteria to utilize ammonia for bacterial protein synthesis.
5.2 Pharmacokinetic properties
Lactulose is poorly absorbed after oral administration and it reaches the colon unchanged. There it is metabolised by the colonic bacterial flora. Metabolism is complete at doses up to 25-50 g or 40-75 ml; at higher dosages, a proportion may be excreted unchanged.
5.3 Preclinical safety data
The results of acute, sub-chronic and chronic toxicity studies in various species indicate that the compound has very low toxicity. The effects observed, appear to be more related to the effect of bulk in the gastrointestinal tract than to a more specific toxic activity. In reproduction and teratology experiments in rabbits, rats or mice no adverse effects were found.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
None
6.2 Incompatibilities
None known.
6.3 Shelf life
36 months unopened
90 days after opening of the bottle
6.4 Special precautions for storage
Do not store above 25°C. Do not refrigerate or freeze.
6.5 Nature and contents of container
Round amber PET bottles containing 200, 300 and 500 ml
Each carton contains one bottle and a 30 ml graduated measuring cup with intermediate graduations of 5 ml.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Medley Pharma Ltd.
Unit 2A, Olympic Way,
Sefton Business Park,
Bootle, Merseyside, L30 1RD,
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 43870/0047
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
15/12/2022
10 DATE OF REVISION OF THE TEXT
20/12/2023