Bromelain + Papain + Rutoside + Trypsin

Usage

This combination of enzymes and a bioflavonoid is primarily prescribed for reducing inflammation and swelling associated with various conditions, including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, post-operative inflammation (e.g., after minor surgery or dental procedures), trauma injuries, edema, and for pain relief (toothache, headache, muscle ache, backache, menstrual cramps).

• Pharmacological Classification: Proteolytic enzymes, anti-inflammatory, anti-edemic, antioxidant.

• Mechanism of Action: Bromelain, trypsin, and papain are proteolytic enzymes that break down proteins, which in turn reduces inflammation and promotes tissue healing. Rutoside, a flavonoid, acts as an antioxidant and anti-inflammatory agent, strengthens blood vessels, and improves circulation. Trypsin, papain, and bromelain increase blood supply to the affected area to promote healing. Rutoside helps by preventing further swelling and inflammation by neutralizing free radicals that cause cell damage.

Alternate Names

Bromelain-Trypsin-Rutoside combination; Proteolytic enzyme combination with Rutoside; Bromelain-Papain-Rutoside-Trypsin combination. Some brand names include: Phlogam, Rutoheal, and Enzictra.

How It Works

• Pharmacodynamics: Bromelain, trypsin, and papain exert their effects by breaking down proteins involved in the inflammatory cascade. Rutoside stabilizes capillary walls, reducing vascular permeability and edema.

• Pharmacokinetics:

  • Absorption: Bromelain is absorbed intact through the gastrointestinal tract (approximately 40%). Trypsin and papain are partially absorbed, likely through peptide transport mechanisms. Rutoside’s absorption is limited (around 17%), occurring primarily in the colon after deglycosylation by gut bacteria.
  • Metabolism: Bromelain is rapidly deactivated in the blood. Trypsin metabolism is not well documented. Rutoside is metabolized to quercetin.
  • Elimination: Some trypsin may be excreted in urine. Elimination pathways for bromelain, papain, and rutoside metabolites are not fully elucidated.

• Mode of Action: Bromelain, trypsin, and papain directly break down inflammatory mediators. Rutoside inhibits the transcription of pro-inflammatory genes.

• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Limited information is available regarding specific receptor interactions or neurotransmitter modulation. The primary mechanism involves enzymatic breakdown of proteins involved in inflammation and oxidative stress.

Dosage

Standard Dosage

Adults: 1-2 tablets two or three times daily. Some sources specify a dosage strength of 48 mg trypsin, 90 mg bromelain, and 100 mg rutoside.

Children: One tablet per 10 kg body weight daily, divided into 2-4 partial doses. Use with caution in children under 12 years of age.

Special Cases:

• Elderly Patients: Use with caution; dose adjustment may be necessary.
• Patients with Renal Impairment: Use with caution; dose adjustment may be necessary.
• Patients with Hepatic Dysfunction: Use with caution; dose adjustment may be necessary.
• Patients with Comorbid Conditions: Use with caution in patients with bleeding disorders, hypertension, or those taking anticoagulants, antibiotics, or antihypertensives.

Clinical Use Cases:

Clinical trials have investigated the use of Bromelain + Trypsin + Rutoside in specific settings such as Temporomandibular Joint Osteoarthritis. Specific dosage recommendations for other clinical settings like intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, and emergency situations are not well-established and require further research.

Dosage Adjustments:

Dosage adjustments may be needed for elderly patients, and those with renal or hepatic impairment. Consult a doctor before consuming alcohol with this medication.

Side Effects

Common Side Effects:

Nausea, vomiting, stomach pain, indigestion, heartburn, stomach upset, diarrhea, and headache.

Rare but Serious Side Effects:

Allergic reactions (skin rash, itching, swelling) and increased risk of bleeding.

Long-Term Effects:

Long-term effects are not well-established.

Adverse Drug Reactions (ADR):

Clinically significant ADRs are rare but may include severe allergic reactions and significant bleeding.

Contraindications

Hypersensitivity to bromelain, trypsin, rutoside, papain, pineapple, or any component of the formulation; hemophilia or other hereditary coagulation disorders; severe liver damage; patients undergoing dialysis; pregnancy; patients with gastrointestinal ulcers.

Drug Interactions

Anticoagulants (e.g., warfarin, aspirin, clopidogrel); antibiotics (e.g., tetracyclines, amoxicillin, sulfonamides); antihypertensives (e.g., benazepril, captopril, enalapril); NSAIDs (e.g., ibuprofen, diclofenac); certain cancer medications (e.g., fluorouracil, vincristine); ginger, garlic, asafoetida, alfalfa, and several other herbs and foods.

Pregnancy and Breastfeeding

This drug is contraindicated during pregnancy due to the risk of miscarriage associated with bromelain. Use with caution during breastfeeding as it is unknown whether the components are excreted in breast milk.

Drug Profile Summary

• Mechanism of Action: Proteolytic and anti-inflammatory action.
• Side Effects: Nausea, vomiting, stomach upset, headache, dizziness.
• Contraindications: Hypersensitivity, bleeding disorders, severe liver disease, pregnancy.
• Drug Interactions: Anticoagulants, antibiotics, antihypertensives, certain herbs and foods.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy, use with caution during breastfeeding.
• Dosage: Adults: 1-2 tablets 2-3 times daily; Children: 1 tablet/10 kg body weight daily.
• Monitoring Parameters: Monitor for signs of bleeding, allergic reactions, and gastrointestinal distress.

Popular Combinations

Diclofenac sodium is sometimes combined with bromelain, trypsin, and rutoside to enhance pain relief and reduce inflammation.

Precautions

• General Precautions: Pre-screening for allergies and bleeding disorders is essential. Use with caution in patients with renal or hepatic impairment, and those taking interacting medications. Avoid alcohol.
• Specific Populations: Pregnant women (contraindicated); breastfeeding mothers (use with caution); children under 12 (use with caution); no specific precautions for elderly or menstruating individuals are explicitly mentioned in the source, but general caution is advised.
• Lifestyle Considerations: Alcohol should be avoided; no specific information about smoking or dietary restrictions is provided in the source, but maintaining a healthy lifestyle is generally recommended. Consult a doctor regarding driving restrictions, as dizziness may occur.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Bromelain + Papain + Rutoside + Trypsin?

A: The standard adult dosage is 1-2 tablets two or three times daily. Children: One tablet per 10 kg body weight daily, divided into 2-4 partial doses. Use with caution in children under 12 years of age. Dosage adjustments may be necessary for elderly patients and those with hepatic or renal impairment.

Q2: How does this drug combination work to reduce inflammation?

A: Bromelain, trypsin, and papain break down proteins involved in the inflammatory process, while rutoside strengthens capillaries and inhibits pro-inflammatory gene transcription.

Q3: What are the common side effects?

A: Common side effects include nausea, vomiting, stomach upset, diarrhea, and headache.

Q4: Is this medication safe during pregnancy?

A: No, it is contraindicated in pregnancy due to the risk of miscarriage associated with bromelain.

Q5: Are there any drug interactions I should be aware of?

A: Yes, this combination may interact with anticoagulants, antibiotics, antihypertensives, NSAIDs, and certain cancer medications. Consult a doctor about other medications and supplements before use.

Q6: Can this drug be used for pain relief?

A: Yes, it is often prescribed for pain associated with inflammation, such as in osteoarthritis, rheumatoid arthritis, or injuries.

Q7: Are there any contraindications for this medication?

A: Yes, contraindications include hypersensitivity to any of the components, bleeding disorders, severe liver disease, and ongoing dialysis.

Q8: What should patients with renal or hepatic impairment do?

A: Patients with renal or hepatic impairment should use this medication with caution and consult their doctor for appropriate dosage adjustments.

Q9: Should I take this medicine with food?

A: This medication can be taken with food to reduce gastrointestinal side effects.