Usage
Diclofenac + Tizanidine is prescribed for the relief of pain and muscle spasms associated with various musculoskeletal conditions, such as:
- Low back pain
- Painful muscle spasms due to spinal disorders
- Spasticity associated with multiple sclerosis or spinal cord injury
- Sprains and strains
- Other acute or chronic musculoskeletal conditions causing pain and spasm
Pharmacological Classification:
- Diclofenac: Non-steroidal anti-inflammatory drug (NSAID)
- Tizanidine: Centrally acting skeletal muscle relaxant, Alpha-2 adrenergic agonist
Mechanism of Action:
This combination medication works through two distinct mechanisms:
- Diclofenac: Inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing the production of prostaglandins, which are mediators of pain, inflammation, and fever.
- Tizanidine: Acts as an alpha-2 adrenergic agonist in the central nervous system (CNS), reducing the release of excitatory neurotransmitters in the spinal cord that contribute to muscle spasm and stiffness. The exact mechanism is presumed to be an increase in presynaptic inhibition of motor neurons.
Alternate Names
There is no internationally recognized non-proprietary name for this combination product. It is most commonly referred to as “Diclofenac + Tizanidine”.
Brand Names: Numerous brand names exist depending on the manufacturer and region; examples include TIDIP. A qualified medical practitioner should consult local formularies or pharmaceutical references for a complete listing of available brand names in their specific region.
How It Works
Pharmacodynamics:
- Diclofenac: Exerts analgesic, anti-inflammatory, and antipyretic effects by inhibiting prostaglandin synthesis.
- Tizanidine: Reduces muscle tone and spasticity by acting on alpha-2 adrenergic receptors in the CNS.
Pharmacokinetics:
- Diclofenac: Well absorbed orally; metabolized in the liver, primarily by CYP2C9; excreted renally.
- Tizanidine: Rapidly absorbed; undergoes extensive hepatic metabolism, primarily by CYP1A2; eliminated via renal excretion.
Mode of Action:
- Diclofenac: Binds to and inhibits COX enzymes, preventing the conversion of arachidonic acid to prostaglandins.
- Tizanidine: Stimulates alpha-2 adrenergic receptors in the spinal cord, decreasing the release of excitatory amino acids, resulting in reduced muscle tone.
Elimination Pathways:
- Diclofenac: Primarily renal excretion of metabolites.
- Tizanidine: Primarily renal excretion of metabolites.
Dosage
Standard Dosage
Adults: The typical starting dose is Diclofenac 50 mg + Tizanidine 2 mg twice daily. The dosage may be adjusted based on individual response and tolerance, up to a maximum of Diclofenac 50 mg + Tizanidine 2 mg three times a day. The total daily dose of Tizanidine should not exceed 36 mg.
Children: Not recommended for use in children under 18 years of age as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Start with a lower dose and titrate cautiously, monitoring renal function.
- Patients with Renal Impairment: Reduced doses are advised; avoid exceeding a total daily dose of 16mg of Tizanidine in severe impairment (creatinine clearance <25 ml/min).
- Patients with Hepatic Dysfunction: Use with extreme caution; monitor liver function closely; this combination is not recommended in cases of severe impairment.
- Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease, gastrointestinal disorders, or bleeding disorders.
Clinical Use Cases
This drug combination is not typically used in clinical scenarios such as intubation, surgical procedures, mechanical ventilation, ICU care, or emergency situations. Its primary indication is the management of musculoskeletal pain and spasms in an outpatient setting.
Dosage Adjustments
Dose adjustments should be made based on patient response, renal or hepatic function, and potential drug interactions. Closely monitor patients for adverse events.
Side Effects
Common Side Effects:
- Dizziness
- Drowsiness
- Dry mouth
- Nausea
- Fatigue
- Headache
- Constipation
Rare but Serious Side Effects:
- Liver damage (hepatotoxicity)
- Allergic reactions
- Blood pressure fluctuations
- Heart rhythm abnormalities
- Gastrointestinal bleeding
Long-Term Effects:
Long-term use may increase the risk of gastrointestinal complications, renal impairment, and cardiovascular events, particularly with Diclofenac.
Adverse Drug Reactions (ADR):
Any signs of hepatotoxicity, severe allergic reactions, or cardiovascular events require immediate discontinuation of the drug and medical intervention.
Contraindications
- Hypersensitivity to diclofenac or tizanidine
- Active peptic ulcer, gastrointestinal bleeding, or perforation
- Severe hepatic impairment
- Severe renal impairment
- History of asthma, urticaria, or allergic-type reactions after taking NSAIDs
- Congestive heart failure (NYHA II-IV)
- Pregnancy (unless benefits clearly outweigh risks)
- Breastfeeding (generally not recommended)
Drug Interactions
- CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin): May increase tizanidine levels.
- Other NSAIDs (e.g., ibuprofen): Increased risk of gastrointestinal bleeding.
- Anticoagulants (e.g., warfarin): Increased bleeding risk.
- Antihypertensives: May potentiate hypotensive effects.
- CNS depressants (e.g., alcohol, benzodiazepines): Increased sedation and drowsiness.
- Alcohol: Exacerbates side effects like drowsiness.
- Fluvoxamine (Luvox): Increases plasma concentration of tizanidine
Pregnancy and Breastfeeding
- Pregnancy: Not recommended unless the potential benefits outweigh the risks. Diclofenac can cause premature closure of the ductus arteriosus in the fetus.
- Breastfeeding: Not recommended as tizanidine is excreted in breast milk and may cause adverse effects in infants.
Drug Profile Summary
- Mechanism of Action: Diclofenac inhibits COX enzymes reducing inflammation and pain; Tizanidine acts as a central alpha-2 adrenergic agonist reducing muscle spasticity.
- Side Effects: Drowsiness, dizziness, dry mouth, nausea, fatigue, gastrointestinal issues, liver dysfunction (rare).
- Contraindications: Hypersensitivity, active peptic ulcer, severe hepatic/renal impairment, pregnancy, breastfeeding.
- Drug Interactions: CYP1A2 inhibitors, other NSAIDs, anticoagulants, antihypertensives, CNS depressants.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: Start with Diclofenac 50 mg/Tizanidine 2 mg twice daily, adjustable based on individual needs, maximum Tizanidine 36 mg/day. Children: Not recommended.
- Monitoring Parameters: Liver function tests, blood pressure, renal function.
Popular Combinations
This combination itself is a commonly prescribed therapy for pain and muscle spasm.
Precautions
- Pre-existing medical conditions should be carefully evaluated.
- Monitor for hepatic and renal function.
- Avoid alcohol.
- Caution while operating machinery or driving.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Diclofenac + Tizanidine?
A: The typical starting dose is Diclofenac 50 mg + Tizanidine 2 mg twice a day. Maximum daily dose of Tizanidine is 36 mg.
Q2: What are the common side effects?
A: Dizziness, drowsiness, dry mouth, nausea, fatigue, and headache are common side effects.
Q3: Can this medication be used during pregnancy?
A: It is generally not recommended during pregnancy unless the benefits outweigh the risks.
Q4: Is it safe to breastfeed while taking this medication?
A: No, it is not generally recommended due to excretion of tizanidine in breast milk.
Q5: What are the significant drug interactions I should be aware of?
A: Interactions can occur with CYP1A2 inhibitors, other NSAIDs, anticoagulants, antihypertensives, and CNS depressants.
Q6: Are there any contraindications to using this combination?
A: Yes. Contraindications include hypersensitivity, active peptic ulcer, severe hepatic or renal impairment, pregnancy, and breastfeeding.
Q7: How does this combination work to relieve muscle spasms and pain?
A: Diclofenac addresses pain and inflammation, while Tizanidine specifically targets muscle spasms by acting on the CNS.
Q8: What should I monitor in patients taking this medication?
A: Closely monitor liver function, renal function, and blood pressure. Look for any signs of gastrointestinal bleeding or allergic reactions.
Q9: Can I prescribe this for children?
A: Safety and efficacy have not been established in children under 18. Therefore it is not recommended.
