Macrogol-Ratiopharm Powder For Oral Solution
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS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 quantitative composition of active ingredients:
Sodium Hydrogen Carbonate 0.1785 g
The content of electrolyte ions per sachet following reconstitution in 125 ml of water is equivalent to:
65 mmol/l 53 mmol/l 17 mmol/l 5 mmol/l
Sodium Chloride
Hydrogen Carbonate (Bicarbonate)
Potassium
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
Macrogol-ratiopharm is for oral use.
Posology:
A course of treatment for chronic constipation with Macrogol-ratiopharm 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 old: Not recommended.
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 any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
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 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 (see section 4.5).
The lemon lime flavour in Macrogol-ratiopharm contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicine
Interaction with other medicinal products and other forms of interaction
4.5
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 withMacrogol-ratiopharm (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 can be used during pregnancy.
Breastfeeding
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 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 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.
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 anaphylaxis,
angioedema, dyspnoea, rash, erythema, urticaria, pruritus
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
General disorders and Peripheral oedema
administration site conditions
4.9 Overdose
Severe 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 and 25 x for faecal impaction. 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 and 1.3 x for faecal impaction. 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
After 24 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
12/02/2015