Tibrolin Tablets

Trypsin, Bromelain and Rutoside Trihydrate Tablets

Each enteric coated tablet contains :

Trypsin BP 48 mg

Bromelain 90 mg

Rutoside Trihydrate BP 100 mg

Excipients q.s.

Colour : Sunset Yellow Lake

Total proteolytic activity not less than 1095 FIP units per tablet (Papain method).

Appropriate overages of enzymes are added to compensate the probable loss on storage

Tablet

4.1 Therapeutic indication

For postoperative inflammation in subject undergoing minor surgery and dental procedure.

4.2 Posology and method of administration

• Adults : 1 to 2 tab b.i.d. or t.i.d. orally
• Children : 1 tab/10 kg body wt, taken daily in 2 - 4 partial doses

Tablets should be swallowed on empty stomach at least 30 min before meals or 2 h after meals.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in the formulation.

4.4 Special warnings and precautions for use

• Should not be used in known cases of hypersensitivity to any of its ingredients.
• Not recommended in patients with hereditary coagulation disorder (e.g. hemophilia) & liver disorder.
• The combination cannot replace an ongoing antibiotic therapy.
• Temporary reduction of dose advised if there is exacerbation of symptoms on initial therapy.

4.5 Drugs interactions

No evidence of incompatibility of Tibrolin with other concomitant medications has been reported.

4.6 Use in special populations

Pregnancy & Breastfeeding

Should be used with caution during pregnancy & breast feeding

4.7 Effects on ability to drive and use machines

It is not known whether Tibrolin tablet alters the ability to drive. Do not drive if you experience any symptoms that affect your ability to concentrate and react.

4.8 Undesirable effects

Generally, well tolerated, even during prolonged high doses were observed in most cases, side effects. Occasionally may appear insignificant change in consistency, colour and odour of stool. Rare side effects are: headache, hunger, and increased sweating. During high-dose were observed feelings of fullness, impoundment, occasional nausea. This feeling can be avoided by dividing the total dose during the day. Rarely occurring allergic reactions (skin rash) disappear after discontinuation

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 email to : medico@zuventus.com

Website : https://www.zuventus.com/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Even if long-term use of higher doses, there were no toxic effects, including possible light diarrhea that after discontinuing the plant disappears spontaneously.

5.1 Mechanism of action

Trypsin is a proteolytic enzyme found in the digestive system where it hydrolyses proteins. Trypsin breaks the fibrin barrier and restores circulation; resolves edema and hematoma; promotes phagocytosis to remove necrotic debris accumulated during injuries and burns; and inhibits necrotic damage and scarring.

Bromelain is a proteolytic enzyme, breaks peptide bonds inside protein molecules. Bromelain assists in removal of blood clot by supporting fibrinolysis, activation of plasmin, preventing aggregation of blood platelets. Bromelain reduces edemas; reduces blood level of plasma kinins to reduce pain; reduces the level of PGE2 and TXA2 in exudates during acute inflammation; induces secretion of interleukin (IL)-1, IL-6, IL-8 & TNF-α to promote re-epithelialization. Bromelain also increases tissue permeability of antibiotics.

Rutoside (also known as Rutin) is the glycoside, formed by combining a disaccharide and flavonol. It is a citrus flavonoid obtained from buckwheat & Pagoda Tree. Rutoside possesses antioxidant, antiinflammatory, antithrombotic, cytoprotective & vasoprotective properties. It promotes wound healing & augments tensile strength of scar tissue significantly. Rutoside also modulates respiratory burst of neutrophils, and inhibits TXA2 formation causing inhibition of platelet aggregation

5.2 Pharmacodynamic properties

The enzymes bromelain and trypsin reduce both edema of inflammatory origin, as well as swelling accompanying trauma or surgery. The enzymes show Fibrinolytic and thrombolytic effect, influence on rheological properties of blood, immunomodulatory effect, analgesic effect.

5.3 Pharmacokinetic properties

Trypsin : Pharmacokinetic study indicates that Trypsin is absorbed by enterocytes, probably through a transcellular route. Radio-labelled human Trypsin metabolism has been investigated in man. Serum half life of Trypsin varies from 17.5-24 minutes. Around 13-38% of the radio-labelled human trypsin injected was recovered from duodenal juice aspirated continuously over 300 minutes. After Radio-labelled Trypsin infusion, 11% of the total dose was found to be present in the circulation after 75 minutes. Metabolism of trypsin has not been well documented. Small amount may be excreted in the urine.

Bromelain : Bromelain is absorbed intact through the gastrointestinal tract. It is reported that about 40% of Bromelain is absorbed from the intestine. The highest concentration of bromelain is found in the blood one hour after administration; however, its proteolytic activity is rapidly deactivated.

Rutoside : Only about 17% of an ingested dose is absorbed. Absorption appears to occur mainly from the colon following the removal of the carbohydrate moiety by bacterial enzymes to form quercetin. Quercetin may undergo glucouronidation in the intestinal cells. Quercetin and glucuronide conjugates of quercetin are transported to the liver via the portal circulation, where they undergo significant first pass metabolism.

Gastric secretions can destroy the Trypsin, Rutoside and Bromelain. The high potency standardized Bromelain, Rutoside and Trypsin formulation is protected from stomach acid by a special enteric coating. This allows high levels of these activated proteolytic enzymes to be absorbed by the mucosal membrane of the intestine.

6.1 Animal toxicology or pharmacology

Acute median lethal dose after oral administration is too high, cannot be given. In vivo chromosomal analyzes :

No statistically significant increase in frequency was observed compared to the control group structural chromosomal aberrations in bone marrow cells.

Embryotoxicity, teratogenicity and impact on pregnancy :

There were no documented deviations from normal during pregnancy, there was no increase in the number intra uterine resorption or fetal death was observed and no malformation. There are changes in the development of organs and during ossification. There were no unexpected changes in the representation of gender or weight of the fruit.

Tibrolin is a combination of two proteases - Trypsin & Bromelain, and a bioflavonoid Rutoside.

Trypsin is a serine protease found in the digestive system, where it cleaves peptide chains, hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin is obtained from the pancreas of pigs by repeated refining and subsequent activation of the proenzyme trypsinogen.

Bromelain is obtained from crude, aqueous extract from the stems and immature fruits of pineapples (Ananas comosus Merr.). Bromelain constitutes an unusually complex mixture of different thiol-endopeptidases and other components such as phosphatases, glucosidases, peroxidases, cellulases, glycoproteins and carbohydrates, among others. In addition, bromelain contains several proteinase inhibitors.

Rutin, also called rutoside, quercetin-3-rutinoside and sophorin, is a citrus flavonoid glycoside found in buckwheat, the leaves and petioles of Rheum species, and asparagus. Rutin is the glycoside between the flavonols quercetin and the disaccharide rutinose.

8.1 Incompatibilities

None

8.2 Shelf-life

24 Months.

8.3 Packaging information

A blister strip of 10 tablets.

8.4 Storage and handing instructions

• Store in a dry & dark place, at a temperature not exceeding 30°C.
• Keep out of reach of children.
• Tablet should be swallowed whole & not to be broken, crushed or chewed.

• Tibrolin should only be used : exactly as prescribed, at the lowest dose possible for your treatment for the shortest time needed,
• Do not take this medicine, if you are allergic to any ingredient of the Tibrolin
• Signs of an allergic reaction include a rash, itching or shortness of breath.
• Advice patients to talk to your doctor or pharmacist, if you get any side effects. This includes any possible side effects not listed in this leaflet.
• Advice patients If they have any further questions, ask doctor or pharmacist.

28 April 2021