butalbital/aspirin/caffeine/codeine

Action and Spectrum

Actions and Spectrum 

Action: 

butalbital: Barbiturate 

aspirin: nonsteroidal anti-inflammatory drug (NSAID)  

caffeine: caffeine is a stimulant that acts on the central nervous system 

codeine: opioid analgesic  

Spectrum: 

The combination of butalbital, aspirin, caffeine, and codeine provides a broader spectrum of action compared to individual components alone.  

It can effectively relieve tension headaches, migraines, and other pain-related muscle tension or inflammation. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

codeine  

Drowsiness 

Constipation 

1-10% 

codeine 

Bradycardia 

Dizziness 

headache 

Hypotension 

confusion 

tachycardia  

lightheadedness 

false feeling of well being 

paradoxical CNS stimulation 

urticaria 

malaise 

restlessness 

rash  

Frequency not defined 

butalbital 

Dizziness 

vomiting 

Sedation 

Drowsiness 

Shortness of breath 

Lightheadedness 

Nausea 

Intoxicated feeling 

Abdominal pain  

aspirin 

Stomach pain 

Nausea 

Dyspepsia 

Tinnitus (high or chronic dose) 

Vomiting 

Rash 

Heartburn 

Urticaria 

caffeine 

Diarrhea 

Tremor 

Tinnitus 

Vomiting 

Nervousness, irritability 

Insomnia, restlessness 

Nausea 

Black Box Warning

Black Box Warning:  

Neonatal opioid withdrawal syndrome 

Life-threatening respiratory depression 

Coadministration with benzodiazepines 

Contraindication / Caution

Contraindication/caution:  

• Bronchospastic reaction to aspirin 
• Respiratory depression 
• Hypersensitivity 
• Known allergy to NSAIDs 
• Peptic ulcer  
• Hemophilia 
• Porphyria 
• Children below 16 years (potential for Reye syndrome) 

Cautions 

• Special attention should be exercised when dealing with cases of gastrointestinal bleeding, especially in patients with a history of GI bleed, alcoholism, or bleeding disorders. 
• Avoid in severe renal impairment (ie, CrCl <10 mL/min) 
• Children can experience Reye syndrome as a result of the aspirin component. It is essential to avoid using aspirin for the treatment of chickenpox or flu symptoms. 
• codeine has been associated with severe respiratory depression and fatal outcomes in pediatric patients, posing a life-threatening risk. 
• The combination of butalbital, aspirin, caffeine, and codeine phosphate can lead to significant hypotension, such as orthostatic hypotension and syncope, in patients who are ambulatory. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is known 

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 a lack of studies on pregnant women and no evidence of risk to the fetus 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 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:  

combining these four ingredients in butalbital/aspirin/caffeine/codeine provides a multimodal approach to pain relief. 

Pharmacodynamics:  

butalbital: Barbiturate,elicits generalized CNS depressant effects 

codeine: analgesic ,Opioid agonist 

caffeine: The vasoconstrictive characteristics of cerebral blood vessels can offer potential benefits in managing headaches. 

aspirin: The action on the hypothalamus leading to the production of antipyresis, as well as the anti-inflammatory effects, are believed to be due to the inhibition of prostaglandin synthetase. This inhibition leads to a reduction in the synthesis of thromboxane A2. 

Pharmacokinetics: 

Absorption 

butalbital: It is well-absorbed orally and reaches peak plasma concentrations within 1 to 2 hours. 

aspirin: aspirin is also well-absorbed orally, with peak plasma concentrations reached within 1 to 2 hours. 

caffeine: It is rapidly and almost completely absorbed after oral administration, with peak plasma concentrations reaching within 30 to 60 minutes. 

codeine: It is well-absorbed orally, and peak plasma concentrations are typically reached within 1 to 2 hours. 

Distribution 

butalbital: It has a moderate volume of distribution, indicating that it is distributed throughout the body. 

aspirin: It has a relatively large volume of distribution, allowing it to distribute extensively into tissues. 

caffeine: It has a large volume of distribution, indicating wide distribution in body tissues. 

codeine: It has a moderate volume of distribution, indicating distribution throughout the body. 

Metabolism 

butalbital: It undergoes hepatic metabolism primarily via the CYP2C19 enzyme. 

aspirin: It is rapidly hydrolyzed to salicylic acid in the body. 

caffeine: It undergoes hepatic metabolism primarily through cytochrome P450 1A2 (CYP1A2). 

codeine: It undergoes hepatic metabolism via CYP2D6 to morphine, which is responsible for its analgesic effects. 

Excretion and Elimination 

butalbital: It is primarily eliminated via hepatic metabolism and subsequent renal excretion of metabolites. 

aspirin: It is excreted mainly through renal elimination as salicylic acid and its metabolites. 

caffeine: It is primarily eliminated through hepatic metabolism and subsequent renal excretion of metabolites. 

codeine: It undergoes renal excretion of unchanged drug and its metabolites. 

Adminstartion

Administration:  

Oral administration of tablets/capsules in a prescribed dosage 

Patient Information Leaflet

Patient information leaflet 

Generic Name: butalbital/aspirin/caffeine/codeine 

Why do we use butalbital/aspirin/caffeine/codeine?  

These combination drugs treat headaches and complex tension (muscle contraction) but can only be used if other non-opioid treatments are incapable.