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Acetaminophen/butalbital/caffeine: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Apr 16, 2020.

1. How it works

  • Acetaminophen/butalbital/caffeine is a combination pain-reliever (analgesic) containing acetaminophen, butalbital, and caffeine.
  • Experts aren't sure exactly how acetaminophen works, but suspect it blocks a specific type of cyclo-oxygenase (COX) enzyme, located mainly in the brain.
  • Butalbital belongs to the class of medicines called barbiturates. When used for pain due to tension headaches, experts believe it works by relaxing muscle contractions and causing sedation via an enhancement of the inhibitory effects of GABA (a neurotransmitter that regulates communication between brain cells).
  • Caffeine is thought to enhance the pain-relieving effects of acetaminophen by up to 40%. In addition, it has vasoconstrictive properties, narrowing blood vessels in the brain thereby decreasing blood flow and oxygen tension (before a headache or a migraine, blood vessels tend to enlarge). This also helps to relieve pain.
  • Acetaminophen/butalbital/caffeine belongs to the class of medicines known as barbiturates because it contains butalbital. It may also be called a combination analgesic.

2. Upsides

  • May be used short-term to relieve episodic tension-type headaches.
  • Generic acetaminophen/butalbital/caffeine is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Dizziness, drowsiness, lightheadedness, sedation, shortness of breath, nausea, vomiting, abdominal pain, or an intoxicated feeling are the most commonly reported side effects.
  • Other side effects, such as constipation, excessive sweating, itch, and mental confusion are less common.
  • Butalbital is habit-forming and there is a high risk of dependence with extended and repeated use of acetaminophen/butalbital/caffeine. Therefore it is not considered a first-choice medicine for headaches.
  • May cause medication-overuse headache with repeated use and a withdrawal syndrome upon discontinuation.
  • The potential for liver damage with the acetaminophen component exists, even at recommended dosages. The risk is increased with higher dosages, with chronic alcohol use, with some medications, and in patients with significant liver disease.
  • May not be suitable for some people, including the elderly and people with kidney or liver disease.
  • Although acetaminophen/butalbital/caffeine may be prescribed for migraine headaches, it is not FDA approved for this use and evidence does not support its use for a migraine.
  • Should not be used during pregnancy or breastfeeding.
  • May interact with a number of other medications including those that also cause sedation such as opioids, benzodiazepines, and sedating antihistamines. Alcohol should be avoided.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

4. Bottom Line

Acetaminophen/butalbital/caffeine may be used for the short-term treatment of tension-type headaches; however, it is not a first-choice medicine because it is potentially habit-forming and causes sedation. Simpler and safer analgesics or analgesic combinations should be tried first.

5. Tips

  • May be administered without regards to food; although food may decrease any reported stomach upset.
  • Do not overuse acetaminophen/butalbital/caffeine because you may become addicted to it and have difficulty stopping it.
  • Over-use of acetaminophen/butalbital/caffeine can also result in a medication-overuse headache (also known as a rebound headache) which occurs when analgesics are taken too frequently to relieve a headache.
  • Never share your acetaminophen/butalbital/caffeine with anybody else.
  • If you have been taking acetaminophen/butalbital/caffeine regularly, or if you think you have become addicted to it, talk to your doctor about slowly withdrawing it, as sudden withdrawal may precipitate a withdrawal syndrome (symptoms include anxiety, dizziness, hallucinations, muscle twitching, nausea, seizures, sleeplessness, or tremor).
  • Acetaminophen/butalbital/caffeine can cause sedation and affect your ability to drive or operate machinery.
  • Do not drink more than two alcoholic drinks a day if you are a man or one alcoholic drink per day if you are women and taking acetaminophen/butalbital/caffeine.
  • Talk to your doctor or pharmacist before taking any other medications or natural products with acetaminophen/butalbital/caffeine as it can interact with a large number of drugs.
  • Talk to your doctor if you have any side effects of concern. Seek urgent medical advice if you develop an allergic-type reaction (difficulty breathing or swallowing, rash, or facial swelling) soon after taking acetaminophen/butalbital/caffeine.
  • Not recommended for women who are pregnant or breastfeeding.
  • Acetaminophen/butalbital/caffeine contains acetaminophen which may be "hidden" in other cough/cold medicines. The total dose of acetaminophen from any source should not exceed 4000mg per day (24 hours).

6. Response and Effectiveness

  • The pain-relieving effects of acetaminophen are reached within 30-60 minutes of administration.
  • Butalbital is well absorbed from the gastrointestinal tract and produces a muscle relaxing effect and sedation within one to two hours. Butalbital is metabolized in the liver by the CYP450 enzyme system which means it has the potential to interact with a large number of other drugs. Butalbital has an average half-life of around 35 hours, which means it lasts for a long time in the body and repeated doses may have a cumulative effect, increasing the risk of side effects.
  • Caffeine is metabolized in the liver to other active substances and has a short half-life (3 to 7 hours).

7. Interactions

Medicines that interact with acetaminophen/butalbital/caffeine may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with acetaminophen/butalbital/caffeine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with acetaminophen/butalbital/caffeine include:

  • antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), or SSRIs (eg, fluoxetine, sertraline)
  • anticonvulsants, such as carbamazepine, divalproex, lamotrigine, phenytoin, phenobarbital, or primidone
  • antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
  • any medication that may cause drowsiness, such as amphetamines, benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, fentanyl or morphine)
  • buprenorphine
  • cannabis
  • cyclosporine
  • dextromethorphan
  • duloxetine
  • heart medications such as diltiazem or verapamil
  • HIV medications such as ritonavir
  • migraine medications, such as ergotamine or dihydroergotamine
  • muscle relaxants, such as cyclobenzaprine
  • naltrexone
  • other medications that contain acetaminophen or an opioid either in combination or as the sole ingredient
  • pentazocine
  • prilocaine
  • rifampin
  • sodium oxybate
  • tamsulosin
  • tramadol
  • warfarin.

Avoid drinking alcohol or taking illegal or recreational drugs while taking acetaminophen/butalbital/caffeine.

Note that this list is not all-inclusive and includes only common medications that may interact with acetaminophen/butalbital/caffeine. You should refer to the prescribing information for acetaminophen/butalbital/caffeine for a complete list of interactions.

References

Butalbital, Acetaminophen, and Caffeine. Revised 11/2019. Drugs.com https://www.drugs.com/ppa/butalbital-acetaminophen-and-caffeine.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use acetaminophen/butalbital/caffeine only for the indication prescribed.

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Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.