tizanidine and rofecoxib

Action and Spectrum

Actions and spectrum: 

tizanidine: 

• Action: tizanidine is a muscle relaxant primarily used to manage muscle spasticity, particularly in multiple sclerosis, spinal cord injuries, or certain neurological disorders. It acts by inhibiting nerve signals sent to the muscles, which helps reduce muscle tension and spasms. 
• Spectrum: tizanidine’s action is specific to the central nervous system, where it targets the alpha-2 adrenergic receptors. It does not possess anti-inflammatory or analgesic properties. 

rofecoxib: 

• Action: It is a nonsteroidal anti-inflammatory drug that belongs to the class of selective COX-2 inhibitors. Its primary action is to reduce inflammation, pain, and fever by inhibiting the enzyme cyclooxygenase 2. COX-2 is involved in the prostaglandins production, which are mediators of inflammation and pain. 
• Spectrum: rofecoxib’s action is anti-inflammatory and analgesic. It is used to manage conditions associated with pain and inflammation, such as osteoarthritis and rheumatoid arthritis. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Diarrhea 

Sore throat 

Runny nose 

Blisters 

Itching 

Pale skin 

Weight gain 

Tiredness 

Back pain 

Constipation 

Cough 

Fever 

Hives 

Swelling 

Hoarseness 

Upset stomach 

painful urination 

Dizziness 

Vomiting 

Dry mouth 

Black Box Warning

Black Box Warning: 

There is no specific black box warning for tizanidine and rofecoxib. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: tizanidine is contraindicated in individuals with a known hypersensitivity to tizanidine or any of the components of the formulation. 
• Cardiovascular Risk: rofecoxib is contraindicated in individuals with a history of heart disease, including heart attack or stroke. It should not be used in patients at high risk of cardiovascular events. 
• Gastrointestinal Bleeding: rofecoxib is contraindicated in individuals with a history of gastrointestinal bleeding or perforation. 
• Pregnancy and Lactation: rofecoxib should not be used during the third trimester of pregnancy, and its use should be avoided during breastfeeding.

Caution: 

• Hypotension: tizanidine may cause hypotension, when going from a sitting or lying position to standing. Caution is advised, and patients should be instructed to rise slowly to minimize the risk of falls or fainting. 
• Hepatic Impairment: tizanidine is metabolized in the liver, so caution is necessary when using it in patients with liver impairment. Lower doses may be required in such cases. 
• Gastrointestinal Risk: Like other NSAIDs (nonsteroidal anti-inflammatory drugs), rofecoxib can increase the risk of gastrointestinal ulcers, bleeding, and perforation. Caution is advised, especially in patients with a history of gastrointestinal problems.

Comorbidities: 

• Liver Disease: tizanidine is metabolized in the liver, so individuals with preexisting liver disease or impaired liver function should use with caution. Lower doses may be required. 
• Renal Impairment: While tizanidine is primarily eliminated in the urine, it is usually not recommended for use in patients with severe renal impairment. 
• Gastrointestinal Disorders: rofecoxib, like other NSAIDs (nonsteroidal anti-inflammatory drugs), can increase the risk of gastrointestinal ulcers and bleeding. It may not be suitable for individuals with a history of gastrointestinal problems. 
• Hypertension: rofecoxib can lead to elevated blood pressure. It should be used cautiously in individuals with hypertension or those at risk of high blood pressure. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: not assigned 

Lactation: excreted into human milk: unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

tizanidine is a centrally acting muscle relaxant. It works by inhibiting nerve signals in the spinal cord that cause muscles to contract. This leads to muscle relaxation, which can help alleviate muscle spasms and stiffness. tizanidine’s effects are primarily targeted at the nervous system and skeletal muscles. 

rofecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that primarily inhibits the activity of an enzyme called cyclooxygenase-2 (COX-2). COX-2 is responsible for production of inflammatory substances called prostaglandins. By reducing prostaglandin production, rofecoxib can relieve pain, reduce inflammation, and lower fever. It was primarily used for conditions associated with inflammation and pain, such as arthritis.  

Pharmacodynamics: 

• Muscle Relaxation: tizanidine acts as a centrally acting muscle relaxant. It primarily works in the central nervous system (CNS) by stimulating alpha-2 adrenergic receptors. By inhibiting nerve signals in the spinal cord that trigger muscle contractions, it leads to muscle relaxation and a reduction in muscle spasms and stiffness. 
• Sedation: tizanidine’s mechanism of action can also lead to sedation (drowsiness) as a side effect. This sedative effect can be beneficial for some individuals but may require caution, particularly when performing tasks that require alertness, such as driving. 
• Anti-Inflammatory Action: rofecoxib belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs). It primarily inhibits the activity of cyclooxygenase-2 (COX-2) enzyme, plays a key role in the prostaglandins production involved in inflammation, pain, and fever. 
• Pain Relief: By reducing the production of prostaglandins, rofecoxib can relieve pain, reduce inflammation, and lower fever. It is particularly effective in managing conditions associated with pain and inflammation, such as arthritis.

Pharmacokinetics: 

tizanidine: 

• Absorption: tizanidine is well absorbed after oral administration, with peak plasma concentrations typically reached within 1-2 hours. The rate and extent of absorption may be affected by food, with higher levels achieved when taken with a meal. 
• Distribution: tizanidine has a small volume of distribution, suggesting that it remains primarily in the bloodstream and does not extensively distribute into tissues. 
• Metabolism: tizanidine undergoes extensive hepatic metabolism, primarily through the cytochrome P450 enzyme system, particularly CYP1A2. Multiple metabolites are formed, some of which are pharmacologically active. Genetic variations in CYP1A2 can influence the metabolism of tizanidine in individuals. 
• Excretion: The metabolites of tizanidine are primarily eliminated in the urine. 

rofecoxib: 

• Absorption: rofecoxib is well absorbed after oral administration. Its absorption is not affected by food. 
• Distribution: rofecoxib is highly protein-bound in the plasma, primarily binding to albumin. This binding can influence its distribution within the body. 
• Metabolism: rofecoxib is metabolized in the liver, primarily by the cytochrome P450 enzyme CYP2C9. Multiple metabolites are formed, some of which are pharmacologically active. 
• Excretion: The metabolites of rofecoxib are primarily eliminated in the urine and feces. 

Adminstartion

Administration: 

• Dosage: The appropriate dosage of tizanidine and rofecoxib will depend on patient’s needs and the severity of their medical condition. The dosages for each component of the combination will be determined by the healthcare provider. 
• Frequency: The frequency of administration, which is how often you take the medication, will also be determined by your healthcare provider. This can vary from once a day to multiple times a day. 
• Duration: The duration of treatment with this combination medication will depend on the medical condition being treated. It is essential to complete the full course, even if symptoms improve before you finish the medication. 
• Route of Administration: tizanidine and rofecoxib can be administered orally, typically in the form of tablets or capsules. Follow the instructions on the medication label regarding how to take them, whether with or without food. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tizanidine and rofecoxib 

Pronounced: (Tie-ZAN-i-deen / Ro-FE-cox-ib)  

Why do we use tizanidine and rofecoxib? 

The combination of tizanidine and rofecoxib is not a common or widely recognized therapeutic regimen. tizanidine is a muscle relaxant, while rofecoxib, which was previously used to treat pain and inflammation, has been withdrawn in many countries due to safety concerns. 

rizanidine is primarily used for the management of muscle spasticity associated with multiple sclerosis, spinal cord injuries, or certain neurological disorders.

It works by inhibiting nerve signals in the spinal cord, leading to muscle relaxation. rofecoxib, on the other hand, was an NSAID used to relieve pain & reduce inflammation in osteoarthritis and rheumatoid arthritis.