1. TRADE NAME OF THE MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One coated tablet contains:
(α-ketoanalogue to DL-isoleucine), calcium-salt 67 mg
(α-ketoanalogue to leucine), calcium-salt 101 mg
(α-ketoanalogue to phenylalanine), calcium-salt 68 mg
(α-ketoanalogue to valine), calcium salt 86 mg
(α-hydroxyanalogue to DL-methionine), calcium-salt 59 mg
L-lysine acetate 105 mg
L-threonine 53 mg
L-tryptophan 23 mg
L-histidine 38 mg
L-tyrosine 30 mg
Total nitrogen content per tablet 36 mg
Calcium content per tablet 1.25 mmol = 50 mg
3. PHARMACEUTICAL FORM
Film coated tablet
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Prevention and therapy of damages due to faulty or deficient protein metabolism in chronic renal insufficiency in connection with limited protein in food of 40 g per day (for adults) and less; i.e. generally in patients with a glomerular filtration rate (GFR) below 25 ml/min.
4.2 Posology and method of administration
For oral use.
If not otherwise prescribed take 4 to 8 tablets three times a day during meals.
This dosage applies to adults (70 kg body weight).
Ketosteril tablets are given as long as the glomerular filtration rate (GFR) is below 25 ml/min and a diet with an intake of max. 40 g protein per day (for adults) is followed.
Hypercalcaemia, disturbed amino acid metabolism.
In case of hereditary phenylketonurie it has to be taken into account that this product contains phenylalanine.
No experience has been made so far with the application in pregnancy and paediatry.
4.4 Special warnings and special precautions for use
Ketosteril should be taken during meals to allow proper absorption and metabolism into the corresponding amino acids. The serum calcium level should be monitored regularly.
Ensure the sufficient supply with calories.
4.5 Interaction with other medicinal products and other forms of interaction
The simultaneous administration of medicaments containing calcium (e.g. acetolyte) may lead to pathological increases of the serum calcium level or intensification thereof.
As the uraemic symptoms improve under Ketosteril, a possible administration of aluminium hydroxide should be reduced. Pay attention to a reduction of serum phosphate.
In order not to interfere with absorption, do not take drugs together with Ketosteril that form sparingly soluble compounds with calcium (e.g. tetracyclines, Chinolone like Ciprofloxacin and Norfloxacin, Iron-, Fluoride- and Estramustin-containing drugs). Between the intake of Ketosteril®-Tablets and drugs from the mentioned categories a period of at least 2 hours should pass.
The susceptibility towards heart/cardiac-active glycosides and hence also the risk of arrhythmia increases with the raise of the blood calcium concentration.
4.6 Pregnancy and lactation
No experience has been made so far with the application in pregnancy and lactation.
4.7 Effects on ability to drive and use machines
4.8 Undesirable effects
Hypercalcaemia may develop. In this case, it is recommended to decrease vitamin D intake.
If the hypercalcaemia persists, reduce the dosage of Ketosteril as well as any other source of calcium.
No symptoms have been observed to date.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Ketosteril allows the intake of essential amino acids while minimising the amino-nitrogen intake.
Following ingestion the keto-analogues are transaminated by taking nitrogen from non-essential amino acids, thereby decreasing the formation of urea by re-using the amino group. The levels of accumulating uremic toxins are decreased. Keto- and/or hydroxy-acids do not elicit hyperfiltration of residual nephrons. Ketoacid-containing supplements have a positive influence on the renal hyperphosphatemia and secondary hyperparathyroidism and can improve renal osteodystrophy. The use of Ketosteril in association with a very low protein diet allows a reduced intake of nitrogen while avoiding the deleterious consequences of inadequate dietary protein intake and malnourishment.
5.2 Pharmacokinetic properties
The plasma kinetics of amino acids and their integration in metabolic pathways are well established. It should nevertheless be noted that, in uremic patients, the plasma disturbances do not seem to depend on digested amino acid intake, and that the post-absorptive kinetics seems to be disturbed very early in the development of the disease.
In normal individuals, there is an increase in the plasma level of keto-analogues, 10 minutes after oral ingestion. These levels reach values that are approximately 5 times higher than the initial level. Peak levels are reached within 20-60 minutes, and normal levels are reached again after 90 minutes. Gastrointestinal absorption is thus very rapid. In the plasma a simultaneous increase in levels of the keto-analogue and the corresponding amino acid show that transamination of the keto-analogues is very rapid. Due to the natural pathways of disposal of alpha-ketonic acids in the organism, it is probable that exogenous intakes are very rapidly integrated into metabolic cycles. Ketoacids follow the same catabolic pathways as the classical amino acids. No specific study on ketoacid excretion has been performed to date.
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of acute and repeated dose toxicity, safety pharmacology and genotoxicity. Ketosteril was found to show no teratogenic property.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Corn starch, crospovidone, talc, silicone dioxide, magnesium stearate, macrogol 6000, quinoline yellow E104, poly[butylmethacrylate-co-(2-dimethylaminoethyl) metha-crylate-co-methylmetha-crylate] 1:2:1 (Eudragit E), triactine, titanium dioxide E171, povidone K-value 29-32
6.4 Special precautions for storage
Do not store above 25° C.
6.5 Nature and contents of container
Pack containing 100 film-coated tablets in blister
6.6 Instruction for use / handling
Do not use Ketosteril after expiry date!
Keep out of the reach of children!
7. MARKETING AUTHORISATION HOLDER
Fresenius Kabi Deutschland GmbH 61346 Bad Homburg v.d.H. Germany Telephone: +49 / 61 72 / 6 86 - 0
This Product Information is valid and approved only in all countries of the European Union. The Product Information applicable in your country may differ from this version. For detailed information valid and approved for your country, please refer to the local/national Fresenius Kabi affiliate.