Usage
This combination medication is primarily prescribed for managing acute musculoskeletal pain and inflammation accompanied by muscle spasms. It is also used in chronic inflammatory conditions.
- Medical Conditions: Low back pain, cervical pain (neck pain), sprains and strains, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, post-operative pain and swelling, dysmenorrhea (painful menstrual cramps).
- Pharmacological Classification: This is a combination product containing a Non-Steroidal Anti-Inflammatory Drug (NSAID) - Diclofenac, a proteolytic enzyme - Serratiopeptidase, and a muscle relaxant - Tizanidine.
- Mechanism of Action: Diclofenac inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis, thereby decreasing pain and inflammation. Serratiopeptidase breaks down fibrin and other proteins involved in inflammation, facilitating fluid drainage and promoting healing. Tizanidine acts centrally as an alpha-2 adrenergic agonist, reducing the release of excitatory neurotransmitters in the spinal cord, leading to muscle relaxation and reduced spasms.
Alternate Names
This combination medication is marketed under various brand names, including Serezon MR, Serfenac-T, and Avadase MR. There is no widely recognized international non-proprietary name (INN) for this specific combination.
How It Works
- Pharmacodynamics: Diclofenac reduces pain and inflammation by inhibiting COX enzymes and prostaglandin synthesis. Serratiopeptidase further reduces inflammation by breaking down proteins like fibrin and bradykinin. Tizanidine reduces muscle spasticity by acting as a central alpha-2 adrenergic agonist, which decreases the release of excitatory neurotransmitters like glutamate and aspartate.
- Pharmacokinetics:
- Diclofenac: Well absorbed orally, metabolized in the liver (primarily by CYP2C9), and excreted primarily through the kidneys.
- Serratiopeptidase: Absorption can vary; it is metabolized in the liver.
- Tizanidine: Extensively metabolized in the liver, primarily by CYP1A2, with renal excretion of metabolites.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Diclofenac inhibits COX-1 and COX-2 enzymes. Tizanidine is an alpha-2 adrenergic agonist. Serratiopeptidase enzymatically degrades bradykinin, fibrin, and other inflammatory mediators.
- Elimination Pathways: Primarily renal excretion for Diclofenac and Tizanidine metabolites, hepatic metabolism for all three components.
Dosage
Standard Dosage
Adults: One tablet twice daily, or as directed by the physician. The usual Diclofenac component is 50mg, Serratiopeptidase is 10-15mg, and Tizanidine is 2mg per tablet.
Children: This combination is generally not recommended for children under 18 years of age. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients: Dose adjustment may be required due to age-related decline in renal and hepatic function. Start with a lower dose and titrate upwards as needed.
- Patients with Renal Impairment: Dose reduction is necessary in patients with moderate to severe renal impairment.
- Patients with Hepatic Dysfunction: Dose adjustment may be needed. Close monitoring of liver function is essential.
- Patients with Comorbid Conditions: Careful consideration is required in patients with cardiovascular disease, hypertension, or gastrointestinal issues, given the potential effects of Diclofenac.
Clinical Use Cases
The combination is not typically employed in the specific clinical settings you mentioned (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations). It’s primarily indicated for managing musculoskeletal pain and inflammation in outpatient settings. Individual components may be used separately in some of those clinical situations but not in this fixed combination.
Dosage Adjustments
Dose modifications are based on patient-specific factors like renal/hepatic dysfunction. Consider reducing the dose or avoiding use altogether.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, headache, dizziness, drowsiness, gastrointestinal discomfort (abdominal pain, dyspepsia, heartburn), dry mouth, fatigue, weakness.
Rare but Serious Side Effects: Allergic reactions (rash, itching, swelling), liver damage (hepatotoxicity), kidney damage (nephrotoxicity), bleeding (gastrointestinal), changes in heart rate (arrhythmia), fluid retention, edema.
Long-Term Effects: Long-term use of NSAIDs like Diclofenac can increase the risk of cardiovascular events and gastrointestinal bleeding.
Adverse Drug Reactions (ADR): Severe allergic reactions (anaphylaxis), Stevens-Johnson Syndrome, gastrointestinal bleeding or perforation, acute renal failure, hepatotoxicity, blood dyscrasias.
Contraindications
- Hypersensitivity to any component of the medication.
- Active peptic ulcer or gastrointestinal bleeding.
- Severe hepatic impairment.
- Severe renal impairment.
- History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
- Pregnancy (especially the third trimester).
- Breastfeeding.
Drug Interactions
- Other NSAIDs: Increased risk of gastrointestinal side effects.
- Anticoagulants (e.g., warfarin): Increased risk of bleeding.
- Antihypertensives: May decrease the effectiveness of these medications.
- CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin): May increase tizanidine levels and enhance side effects.
- Alcohol: May increase drowsiness and the risk of gastrointestinal side effects.
- CNS Depressants: Increased sedation with other medications like benzodiazepines and opioids.
- CYP2C9 Inhibitors/Inducers: May affect Diclofenac metabolism.
Pregnancy and Breastfeeding
This combination is contraindicated during pregnancy, especially in the third trimester, and during breastfeeding due to potential risks to the fetus or neonate. Diclofenac is associated with premature closure of the ductus arteriosus in the fetus. Tizanidine’s effects on a developing fetus or nursing infant are not well established.
Drug Profile Summary
- Mechanism of Action: Diclofenac inhibits COX enzymes; serratiopeptidase breaks down inflammatory proteins; tizanidine acts as a central muscle relaxant.
- Side Effects: See above.
- Contraindications: See above.
- Drug Interactions: See above.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: See above.
- Monitoring Parameters: Liver and kidney function, blood pressure, signs of gastrointestinal bleeding. Complete blood count (CBC) with differential if concerned about blood dyscrasias.
Popular Combinations
While diclofenac and tizanidine are sometimes used together, the addition of serratiopeptidase to this combination is less well-established. Data supporting the efficacy and safety of the triple combination is limited.
Precautions
- General Precautions: Evaluate pre-existing medical conditions (cardiovascular disease, hypertension, renal/hepatic impairment) before initiating therapy. Screen for allergies to any component.
- Specific Populations: See above for pregnancy, breastfeeding, children, and elderly.
- Lifestyle Considerations: Avoid alcohol consumption during treatment. May cause drowsiness; avoid driving or operating machinery if affected.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Diclofenac + Serratiopeptidase + Tizanidine?
A: The typical adult dosage is one tablet twice daily, but this can be adjusted based on individual patient needs and tolerability. It is not recommended for children under 18. Elderly patients and those with hepatic or renal impairment may require dose adjustments.
Q2: Can this combination be used during pregnancy or breastfeeding?
A: No, it’s contraindicated in both pregnancy (especially the third trimester) and breastfeeding due to potential risks to the fetus or neonate.
Q3: What are the most common side effects?
A: Common side effects include nausea, vomiting, diarrhea, dizziness, drowsiness, headache, and gastrointestinal discomfort.
Q4: Are there any serious side effects I should be aware of?
A: Yes, though rare, serious side effects can include allergic reactions, liver or kidney damage, and gastrointestinal bleeding. Patients should be monitored for these.
Q5: What medications should be avoided while taking this combination?
A: Avoid other NSAIDs, anticoagulants, antihypertensives, and CYP1A2 inhibitors. Alcohol should also be avoided. Consult a doctor or pharmacist about any potential interactions with other medications.
Q6: Can this combination be used long-term?
A: Long-term use should be carefully considered and monitored due to potential risks, especially with Diclofenac’s association with cardiovascular and gastrointestinal issues. It should be used for the shortest duration necessary to control symptoms.
Q7: How does tizanidine contribute to this combination?
A: Tizanidine is a muscle relaxant that helps relieve muscle spasms and spasticity often associated with musculoskeletal pain.
Q8: What is the role of serratiopeptidase in this medication?
A: Serratiopeptidase is a proteolytic enzyme believed to have anti-inflammatory effects by breaking down proteins involved in the inflammatory process. However, evidence supporting its clinical efficacy in this combination is limited.
Q9: Can I take this medication if I have a history of peptic ulcers?
A: No, active peptic ulcer disease or a history of gastrointestinal bleeding is a contraindication for this medication due to the Diclofenac component.
