celecoxib/tramadol

Action and Spectrum

Actions and Spectrum: 

A nonsteroidal anti-inflammatory medicine (NSAID), celecoxib blocks the production of prostaglandins, which are responsible for inflammation and discomfort, by inhibiting the enzyme cyclooxygenase-2 (COX-2).

The main conditions for which celecoxib is prescribed include osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute pain. 

tramadol, on the other hand, blocks the transmission of pain signals by binding to the mu-opioid receptor in the brain and spinal cord. It is a centrally acting opioid analgesic. tramadol is used to treat moderate to severe pain, including cancer pain, post-operative pain, and neuropathic pain. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

Decreased appetite (3.3%) 

Somnolence (8.2%) 

>10% 

Nausea (30.1%) 

Headache (11.5%) 

Dizziness (16.9%) 

Vomiting (15.8%) 

Post marketing reports 

Hypoglycemia 

Movement disorder, speech disorder 

Androgen deficiency 

Hypoglycemia, hyponatremia 

Fatal intracranial hemorrhage 

Interstitial nephritis 

Anaphylactoid reaction, angioedema 

Aseptic meningitis, ageusia, anosmia 

Liver necrosis, hepatitis  

Pancytopenia, leukopenia 

Severe hyponatremia 

Miosis, mydriasis 

Jaundice, hepatic failure 

Agranulocytosis, aplastic anemia  

Serotonin syndrome 

Delirium 

Adrenal insufficiency 

QT prolongation

Black Box Warning

Black Box Warning 

A higher risk of cardiovascular events, including heart attacks and strokes, is included in the black box warning for celecoxib.  

Since tramadol is an opioid, it can be abused and lead to addiction just like other opioids. tramadol use can result in physical or psychological dependence in patients and abuse can cause overdose and death. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication for celecoxib: 

• celecoxib or any other NSAID hypersensitivity 
• History of adverse reaction to aspirin or other NSAIDs, including asthma, urticaria, or other allergy-type reactions 
• When undergoing coronary artery bypass graft (CABG) surgery 

Caution for tramadol: 

• Cardiovascular events are more likely (as indicated in the black box warning) 
• GI bleeding, ulcers, and perforations, which can happen without any prior symptoms 
• Hepatic dysfunction 
• Renal dysfunction 
• Dehydration 
• Patients who are elderly may be more susceptible to side effects, such as renal toxicity and gastrointestinal haemorrhage. 

Contraindication for tramadol: 

• hypersensitivity to opioids, including tramadol 
• Use in patients receiving or just getting from monoamine oxidase inhibitors (MAOIs) 
• respiratory sadness that is severe 
• asthma that is acute or severe, hypercapnia, or hypoxia 
• gastrointestinal blockage, including paralytic ileus, that is either known or suspected 

Caution for tramadol: 

• Risk of respiratory depression, particularly in old and weakened individuals and those with respiratory conditions 
• Seizure risk, especially at higher doses or in individuals with a history of epilepsy or seizures 
• Serotonin syndrome risk, especially when used with other serotonergic medications 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excretion into human milk is known (at low levels for both celecoxib and tramadol) 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.   

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 available 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 

A nonsteroidal anti-inflammatory medicine (NSAID), celecoxib selectively inhibits the COX-2 enzyme, which oversees generating prostaglandins that cause inflammation and pain.  

As an opioid analgesic, tramadol blocks the transmission of pain signals by attaching to the mu-opioid receptor in the central nervous system. As tramadol also prevents serotonin and norepinephrine from being reabsorbed, which may help explain why it has analgesic effects. 

Pharmacodynamics 

The COX-1 enzyme, which is necessary for the creation of prostaglandins that protect the gastrointestinal tract and manage renal blood flow, is not severely inhibited by celecoxib.  

In comparison to other opioids like morphine, tramadol has a reduced affinity for the mu-opioid receptor, which may help explain why it is less likely to be abused and become addictive. 

Pharmacokinetics 

Absorption  

After oral administration, celecoxib is effectively absorbed from the digestive system, with a bioavailability of about 40 to 50%. Celecoxib is not influenced by food in terms of absorption, but when it is taken with food, the peak plasma concentration is postponed by roughly 1 to 2 hours. Following oral administration, tramadol is quickly absorbed from the digestive system and has a bioavailability of about 70%. Food has no impact on how well tramadol is absorbed. 

Distribution 

celecoxib has a volume of distribution of around 400 litres and is largely protein-bound (about 97%). The anti-inflammatory properties of celecoxib are present in the synovial fluid of joints, where it is broadly dispersed throughout the body. tramadol has a volume of distribution of about 2.6 litres per kilogramme and is also very protein bound. The effects of tramadol on pain are felt throughout the body, including in the brain. 

Metabolism 

celecoxib is largely broken down into two primary metabolites in the liver by cytochrome P450 enzymes, especially CYP2C9. These two primary metabolites are then further broken down and removed in the urine and feces. celecoxib has a half-life of approximately 11 hours.

The cytochrome P450 enzymes CYP2D6 and CYP3A4 metabolise tramadol in the liver to create active and inactive metabolites. O-desmethyltramadol (M1), the active metabolite of tramadol, is a strong mu-opioid receptor agonist and greatly contributes to the analgesic effects of the drug. tramadol has a half-life of roughly 6 hours. 

Elimination and excretion 

celecoxib and its metabolites are excreted in the urine, with 27% of the dose being excreted unchanged and 67% of the dose being excreted as metabolites. The tramadol and its metabolites are likewise excreted in the urine, with around 30% of the dosage being removed unaltered and about 60% being eliminated as metabolites. 

Adminstartion

Administration:  

celecoxib and tramadol are both available in oral formulations as capsules and tablets forms. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: celecoxib/tramadol 

Why do we use celecoxib/tramadol? 

For celecoxib: 

Treatment of rheumatoid arthritis and osteoarthritis 

Treatment of dysmenorrhea and severe discomfort 

Patients with familial adenomatous polyposis should avoid developing colon polyps.  

Acute gouty arthritis treatment 

For tramadol: 

To treat moderate to severe pain 

Management of chronic pain 

Ache that is neurotic 

Pain control following surgery, an injury or dental work