Ketoxil

Pink Coloured, elongated shaped biconvex, film coated tablets, scored on one side, plain on other side.
Each Film-coated tablet contains: Calcium-4-methyl-2-oxovalerate 101 mg (a-ketoanalogue to leucine, Calcium salt), Calcium-3-methyl-2-oxobutyrate 86 mg (a-ketoanalogue to valine, Calcium salt), Calcium-2-oxo-3-phenylpropionate 68 mg (a-ketoanalogue to phenylalanine, Calcium salt), Calcium-3-methyl-2-oxovalerate 67 mg (a-ketoanalogue to isoleucine, Calcium salt), Calcium-DL-2-hydroxy-4-(methylthio) butyrate 59 mg (a-hydroxyanalogue to methionine, Calcium salt), L-Lysine Acetate 105 mg, L-Threonine 53 mg, L-Histidine 38 mg, L-Tyrosine 30 mg, L-Tryptophan 23 mg.

Pharmacotherapeutic group: Amino acids, including combinations with polypeptides.
Pharmacology: Pharmacodynamics: Ketoanalogues + Essential Amino Acids (Ketoxil) tablets are administered for nutrition therapy in chronic kidney disease.
Ketoanalogues + Essential Amino Acids (Ketoxil) allows the intake of essential amino acids while minimizing the amino-nitrogen intake.
Following absorption, the keto- and hydroxy-analogues are transaminated to the corresponding essential amino acids by taking nitrogen from non-essential amino acids, thereby decreasing the formation of urea by re-using the amino group. Hence, the accumulation of uremic toxins is reduced. Keto and hydroxy acids do not induce hyperfiltration of the residual nephrons. Ketoacid containing supplements exert positive effect on renal hyperphosphatemia and secondary hyperparathyroidism. Moreover, renal osteodystrophy may be improved. The use of Ketoanalogues + Essential Amino Acids (Ketoxil) in combination with a very low protein diet allows to reduce nitrogen intake while preventing the deleterious consequences of inadequate dietary protein intake and malnutrition.
Pharmacokinetics: The plasma kinetics of amino acids and their integration in the metabolic pathways are well established. It should nevertheless be noted that in uremic patients, the cause of the changed plasma levels, which occur frequently in these patients, does not seem to be the absorption of the supplied amino acids, i.e. the absorption itself is not disturbed. The changed plasma levels seem to be due to impaired post-absorptive kinetics, which can be detected in a very early stage of a disease.
In healthy individuals, the plasma levels of ketoacids increase within 10 min after oral administration. Increases of up to the 5-fold the baseline levels are achieved. Peak levels occur within 20-60 min, and after 90 min levels stabilize in the range of the base levels.
Gastrointestinal absorption is thus very rapid. The simultaneous increases in the levels of the ketoacids and the corresponding amino acids show that the ketoacids are transaminated very rapidly. Due to the physiological utilization pathways of ketoacids in the body it is likely that exogenously supplied ketoacids are very rapidly integrated into the metabolic cycles. Ketoacids follow the same catabolic pathways as classical amino acids. No specific study on ketoacid excretion has been performed to date.

Prevention and treatment of damages due to faulty or deficient protein metabolism in chronic renal insufficiency in connection with limited protein in food of 40 g/day (for adults). Usually this applies to patients whose glomerular filtration rate (GFR) is less than 25 mL/min.

If not otherwise prescribed, the dose for adults (70 kg body weight) is 4 to 8 tablets three times daily during meals. The tablets must not be chewed.
Ingestion during meals facilitates proper absorption and metabolization into the corresponding amino acids.
There is no experience in children.
For oral use.
Duration of application: The product is administered as long as the glomerular filtration rate (GFR) is below 25 mL/min, and concomitantly, dietary protein is restricted to 40 g/day or less (for adults).

No case of overdose has been reported.

Hypersensitivity to the active substances or to any of the excipients.
Hypercalcemia.
Disturbed amino acid metabolism.

The serum calcium level should be monitored regularly. Ensure sufficient calorie intake. No experience has been gained so far with the administration in pediatric patients.
In the presence of hereditary phenylketonuria, attention should be given to the fact that Ketoxil contains phenylalanine. Monitoring of the serum phosphate levels is needed in case of concomitant administration of aluminum hydroxide.

There are no adequate data from the use of Ketoanalogues + Essential Amino Acids (Ketoxil) in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development. Caution should be exercised when prescribing to pregnant women. No experience has been made so far with the use during lactation.

Metabolism and nutrition disorders: Very rare: hypercalcemia.
If hypercalcemia occurs, the intake of vitamin D should be reduced. In case of persisting hypercalcemia, the dose of the product as well as the intake of any other calcium sources has to be reduced.

Concomitant administration of calcium-containing drugs may cause or aggravate elevated serum calcium levels.
Drugs that form hard soluble compounds with calcium (e.g. tetracyclines, quinolones such as ciprofloxacin and norfloxacin as well as drugs containing iron, fluoride or estramustine) should not be taken at the same time with Ketoanalogues + Essential Amino Acids (Ketoxil) to avoid disturbed absorption of the active substance. An interval of at least two hours should elapse between the ingestion of Ketoanalogues + Essential Amino Acids (Ketoxil) and these drugs.
The susceptibility to cardioactive glycosides, and hence the risk for arrhythmia will increase since Ketoanalogues + Essential Amino Acids (Ketoxil) produces elevated serum calcium levels. Uremic symptoms improve under therapy with Ketoanalogues + Essential Amino Acids (Ketoxil). Thus, in case of aluminium hydroxide administration, the dose of this drug has to be reduced if necessary. Serum phosphate levels should be monitored for a decrease.

Store at temperatures not exceeding 30°C.

Other Drugs Acting on the Genito-Urinary System

V06DE - Amino acids/carbohydrates/minerals/vitamins, combinations ; Used as general nutrients.

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