Macrogol-Ratiopharm Powder For Oral Solution
SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT
Macrogol-ratiopharm powder for oral solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each sachet contains the following active substances:
Sodium hydrogen carbonate 0.1785 g
The content of electrolyte ions per sachet when made up to 125 ml of solution is as follows:
65 mmol/l 53 mmol/l 17 mmol/l 5 mmol/l
Sodium Chloride
Hydrogen carbonate Potassium
Excipient with known effect: sorbitol For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Powder for oral solution
Single-dose sachet containing a free flowing white powder.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the treatment of chronic constipation
4.2 Posology and method of administration
Posology
A course of treatment for chronic constipation with Macrogol-ratiopharm powder for oral solution does not normally exceed 2 weeks, although this can be repeated if required.
As for all laxatives, prolonged use is not usually recommended. Extended use may be necessary in the care of patients with severe chronic or resistant constipation, secondary to multiple sclerosis or Parkinson's Disease, or induced by regular constipating medication in particular opioids and antimuscarinics.
Adults, adolescents and the elderly: 1-3 sachets daily in divided doses, according to individual response. For extended use, the dose can be adjusted down to 1 or 2 sachets daily.
Children (below 12 years of age): Not recommended. Alternative products are available for children.
Patients with renal insufficiency: No dosage change is necessary.
Method of administration
Each sachet should be dissolved in 125 ml water.
4.3 Contraindications
Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, ileus severe inflammatory conditions of the intestinal tract such as Crohn’s disease and ulcerative colitis and toxic megacolon.
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
The fluid content of Macrogol- ratiopharm powder when re-constituted with water does not replace regular fluid intake and adequate fluid intake must be maintained.
Mild adverse drug reactions are possible as indicated in section 4.8. If patients develop any symptoms indicating shifts of fluids/electrolytes (e.g. oedema, shortness of breath, increasing fatigue, dehydration, cardiac failure) Macrogol-ratiopharm powder for oral solution should be stopped immediately and electrolytes measured and any abnormality should be treated appropriately.
The absorption of other medicinal products could transiently be reduced due to an increase in gastro-intestinal transit rate induced by Macrogol-ratiopharm powder for oral solution (see section 4.5).
This medicine contains 0.63 mmol (25 mg) potassium per sachet. This should be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.
This medicine contains 8.1 mmol (187 mg) sodium per sachet. This should be taken into consideration by patients on a controlled sodium diet.
The lemon lime flavour in Macrogol-ratiopharm powder for oral solution
contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Macrogol 3350 raises the solubility of medicinal products that are soluble in alcohol and relatively insoluble in water.
There is a possibility that the absorption of other medicinal products could be transiently reduced during use with Macrogol-ratiopharm powder for oral solution (see section 4.4).
There have been isolated reports of decreased efficacy with some concomitantly administered medicinal products, e.g. anti-epileptics.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are limited amount of data from the use of macrogol 3350 in pregnant women.
Studies in animals have shown indirect reproductive toxicity (see section 5.3). Clinically, no effects during pregnancy are anticipated, since systemic exposure to macrogol 3350 is negligible.
Macrogol-ratiopharm powder 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 macrogol 3350 is negligible. Macrogol-ratiopharm powder for oral solution can be used during breast-feeding.
Fertility
There are no data on the effects of macrogol 3350 on fertility in humans. There were no effects on fertility in studies in male and female rats (see section 5.3).
4.7 Effects on ability to drive and use machines
Macrogol-ratiopharm powder for oral solution has no influence on the ability to drive and use machines.
4.8 Undesirable effects
Reactions related to the gastrointestinal tract occur most commonly.
These reactions may occur as a consequence of expansion of the contents of the gastrointestinal tract, and an increase in motility due to the pharmacologic effects of Macrogol-ratiopharm powder for oral solution.
Mild diarrhoea usually responds to dose reduction.
The frequency of the adverse effects is not known as it cannot be estimated from the available data.
System Order Class Adverse Events
Immune system disorders Allergic reactions, including anaphylactic reactions, dyspnoea and skin reactions (see below)
Metabolism and nutrition disorders Electrolyte disturbances, particularly hyperkalaemia and hypokalaemia
Nervous system disorders Headache
Gastrointestinal disorders Abdominal pain, diarrhoea, vomiting, nausea,
dyspepsia, abdominal distension, borborygmi, flatulence, anal discomfort
Skin and subcutaneous tissue disorders Allergic skin reactions, including angioedema, urticaria, pruritus, rash, erythema
General disorders and administration site conditions Peripheral oedema
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 at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Severe abdominal pain or distension can be treated by nasogastric aspiration. Extensive fluid loss by diarrhoea or vomiting may require correction of electrolyte disturbances.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Osmotically acting laxatives.
ATC code: A06A D65
Macrogol 3350 acts by virtue of its osmotic action in the gut, which induces a laxative effect. Macrogol 3350 increases the stool volume, which triggers colon motility via neuromuscular pathways. The physiological consequence is an improved propulsive colonic transportation of the softened stools and a facilitation of the defaecation. Electrolytes combined with macrogol 3350 are exchanged across the intestinal barrier (mucosa) with serum electrolytes and excreted in faecal water without net gain or loss of sodium, potassium and water.
Clinical studies using the listed active substances for the treatment of chronic constipation have shown that the dose needed to produce normal formed stools tends to reduce over time. Many patients, respond to between one and two sachets a day, but this dose should be adjusted depending on individual response.
5.2 Pharmacokinetic properties
Macrogol 3350 is unchanged along the gut. It is virtually unabsorbed from the gastrointestinal tract. Any macrogol 3350 that is absorbed is excreted via the urine.
5.3 Preclinical safety data
Preclinical studies provide evidence that macrogol 3350 has no significant systemic toxicity potential, based on conventional studies of pharmacology, repeated dose toxicity and genotoxicity
There were no direct embryotoxic or teratogenic effects in rats even at maternally toxic levels that are a multiple of 66 x the maximum recommended dose in humans for chronic constipation. Indirect embryofoetal effects, including reduction in fetal and placental weights, reduced fetal viability, increased limb and paw hyperflexion and abortions, were noted in the rabbit at a maternally toxic dose that was 3.3 x the maximum recommended dose in humans for treatment of chronic constipation. Rabbits are sensitive animal test species to the effects of GI-acting substances and the studies were conducted under exaggerated conditions with high dose volumes administered, which are not clinically relevant. The findings may have been a consequence of an indirect effect of macrogol 3350 related to poor maternal condition as the result of an exaggerated pharmacodynamic response in the rabbit. There was no indication of a teratogenic effect.
There are long-term animal toxicity or carcinogenicity studies involving macrogol 3350. Results from these and other toxicity studies using high levels of orally administered high-molecular weight macrogols provide evidence of safety at the recommended therapeutic dose.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Silica colloidal anhydrous Saccharin sodium Orange flavour
(Orange flavour contains: flavouring preparations and substances, natural flavouring substances, maltodextrin, acacia gum, a-tocopherol)
Lemon lime flavour (Lemon lime flavour contains: natural lemon oil, natural powder flavour lemon, powder flavour lime, maltodextrin, mannitol, gluconolactone, sorbitol [E420], acacia gum, silica colloidal anhydrous)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
30 months
Reconstituted solution: 24 hours
6.4 Special precautions for storage
Sachet: Do not store above 25 °C.
Reconstituted solution: Store covered in a refrigerator (2°C to 8°C).
6.5 Nature and contents of container
The sachet is composed of paper, ethylene/methacrylic acid co-polymer and aluminium.
Sachets are packed in cartons of 2, 6, 8, 10, 20, 30, 50, 60 (2x30) and 100 (2x50). Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Preparation of solution:
The content of each sachet should be dissolved in 125 ml water.
After six hours, any unused solution should be discarded.
7 MARKETING AUTHORISATION HOLDER
ratiopharm GmbH, Graf-Arco-Str.3, 89079 Ulm, Germany
8
MARKETING AUTHORISATION NUMBER(S)
PL 15773/0853
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
12/10/2010
10 DATE OF REVISION OF THE TEXT
23/11/2016