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Three Rx pill bottles: Pregabalin interactions
Drug Info

Pregabalin interactions to avoid

In addition to interactions with other medications, pregabalin can also interact with alcohol and cannabinoid-containing products
Stephanie Melby, PharmD, medical writer and reviewer for SingleCare
By | Jan. 12, 2024

Key takeaways

  • Pregabalin causes sedation, and certain drug interactions can further increase tiredness, dizziness, or drowsiness, leading to dangerous falls or accidental injuries.

  • Taking pregabalin with other central nervous system (CNS) depressants or alcohol can increase the risk of dangerous sedation, leading to respiratory depression (slow or shallow breathing), falls, or accidental injuries.

  • Pregabalin can increase the risk of a type of skin reaction called angioedema, the swelling in the deep layers of the skin commonly occurring in the eyelids, mouth, or genitals. Certain drug interactions may enhance the risk of this side effect.

  • Older adults (people who are older than 65 years) have a greater risk of serious sedation adverse effects from pregabalin drug interactions.

  • To avoid unwanted drug interactions, healthcare providers can review medication lists and make necessary adjustments.

  • If a dangerous mixture of medications has been consumed, seek immediate medical help or contact Poison Control for help.

Drug interactions | Other interactions | Avoiding interactions | When to see a doctor

Pregabalin (brand name Lyrica) is a prescription medication that is a type of anticonvulsant drug used for treating a variety of conditions, including partial-onset seizures, fibromyalgia, nerve pain associated with diabetic peripheral neuropathy, nerve pain associated with spinal cord injury, and pain following a shingles infection (postherpetic neuralgia).

Pregabalin can interact with opioids, benzodiazepines, muscle relaxants, antihistamines, sleep medications, and certain blood pressure medications, among other drug classes. Do not take pregabalin with Astepro (azelastine), olopatadine, or orphenadrine without consulting a healthcare professional. Pregabalin also interacts with alcohol.

It’s important to be aware of pregabalin interactions as other drugs can affect pregabalin’s effectiveness and cause or worsen side effects. As a medication that can cause sedation, drug interactions with pregabalin are very crucial to avoid, as increased drowsiness and dizziness can put people at risk.

RELATED: Lyrica side effects and interactions and how to avoid them

Pregabalin drug interactions

There are a variety of prescription drugs that can interact with pregabalin, including opioids, benzodiazepines, muscle relaxants, antihistamines, sedatives, and certain blood pressure medications.

Opioids

Opioids are prescription medications that are analgesics (pain relievers) that can slow down the central nervous system (CNS), like pregabalin. Opioids can be used to help manage pain that is typically moderate to severe rather than pain that can be managed with treatments such as over-the-counter (OTC) medications. Severe and potentially life-threatening drug interactions can occur if pregabalin is taken with an opioid. This drug interaction could lead to excessive depression of the central nervous system, such as respiratory depression, hypotension (low blood pressure), sedation, or coma.

It’s recommended that healthcare providers either avoid this combination or consider a dose reduction of one or both medications followed by close monitoring. There are alternative pain relievers that can be taken if an opioid needs to be avoided, such as acetaminophen or NSAIDs (such as ibuprofen or naproxen). It’s essential for patients and caregivers to monitor for signs and symptoms of a dangerous interaction, such as difficulty breathing, slowed breathing, other breathing problems, or excessive sedation. Seek immediate medical attention if there are signs and symptoms of this interaction.

Examples of common opioids include:

Benzodiazepines

Benzodiazepines are prescription medications that are another type of central nervous system depressant. Benzodiazepines are used for a variety of conditions, including anxiety disorders, insomnia, agitation, seizure disorders, acute status epilepticus, amnesia initiation, and spastic disorders. Taking benzodiazepines and pregabalin together has the potential for severe and potentially life-threatening drug interactions because of excessive depression of the central nervous system. The risks of this drug interaction are similar to the interaction with opioids and are true for other medications that depress the central nervous system.

Possible symptoms of this drug interaction include confusion, impaired coordination, drowsiness, lightheadedness, weakness, and respiratory depression. It’s recommended that healthcare providers use caution and monitor therapy if pregabalin and benzodiazepine are prescribed together. Providers can also consider a dose reduction of one or both drugs. Again, it is important to always be on alert for signs and symptoms of drug interaction and seek immediate medical attention if needed.

Examples of common benzodiazepines include:

Muscle Relaxants

Muscle relaxants are prescription medications that can treat various painful musculoskeletal conditions. People may use these medications for muscle spasms, muscle strains, muscle sprains, and muscle-related injuries. Many muscle relaxants relax the muscles in the body by depressing the central nervous system (CNS), which allows the body to relax. Similarly to opioids and benzodiazepines, taking pregabalin with muscle relaxants can cause excessive drowsiness, confusion, weakness, poor muscle control, and even respiratory depression.

Management of musculoskeletal conditions includes physical therapy and increased rest to help treat pain and relieve discomfort. These techniques and OTC pain relievers can be considered alternatives. However, if treatment with a muscle relaxant is necessary, people should continue to use caution when taking both medications and healthcare providers should monitor therapy. Dose reductions of one or both medications should be considered. However, there is one muscle relaxant called orphenadrine that should not be used with pregabalin as the drug manufacturer explicitly states in the medication guide to avoid taking orphenadrine with central nervous depressants. Patients and caregivers should continue to look out for signs and symptoms of drug interaction and seek immediate medical attention if needed.

Examples of common muscle relaxants include:

Antihistamines

Antihistamines are commonly used medications available as OTC and prescription that can help relieve allergy symptoms and itching due to hives. Some antihistamines are used as sleep aids and motion sickness treatments. When antihistamines are taken with a central nervous system depressant like pregabalin, there is the potential for added depressant effects like drowsiness, weakness, confusion, poor muscle control, and possibly respiratory depression. Older antihistamines, such as diphenhydramine and doxylamine, are more commonly associated with sedation and nervous system depression.

Since many antihistamines are available as OTC medications and are easily accessible at pharmacies and convenience stores, this potential drug interaction may be missed by a doctor or nurse at medical appointments. Pharmacists are great resources for providing medical advice and educating the public about possible drug interactions. When starting new medications like pregabalin, remember to ask a pharmacist about serious side effects and the safety of taking certain medications together. People should use caution when taking antihistamines and pregabalin together. Healthcare providers can also consider dose reductions of one or both drugs. There are two nasal antihistamines called Astepro (azelastine) and olopatadine that should not be used with pregabalin as each of the drug manufacturers explicitly states to avoid using central nervous depressants.

Examples of common antihistamines include:

Sleep Medications

Sleep medications can help people either fall asleep more easily or stay asleep throughout the night, so these medications should always be used cautiously with other medications that can cause drowsiness. The non-benzodiazepine sleep aids (also called z-drugs) work to slow down the nervous system and pose a risk of too much nervous system depression when taken with pregabalin. Signs of a possible interaction include excessive sedation and psychomotor impairment (slowing down of thought and physical movements).

Other sleep hygiene practices can be considered. However, if sleep aid treatment is necessary, people should use caution when combining these medications, and healthcare providers should monitor therapy. Additionally, doctors should consider a dose reduction of one or both drugs to lessen the effects of a possible interaction. This drug interaction has been associated with next-day driving impairment and an increased risk for complex behaviors such as “sleep-driving.”

Examples of common Z-drugs include:

Certain Blood Pressure Medications (ACE inhibitors)

ACE-Inhibitors are a type of blood pressure medication that can help manage several conditions, including hypertension (high blood pressure), heart failure, and coronary artery disease. While common side effects of ACE inhibitors include dizziness, low blood pressure, and cough, angioedema is a less common side effect. Angioedema is swelling in the deep layers of the skin and is often seen with hives. It most commonly occurs in the eyelids, mouth, or genitals. Sometimes, it is associated with an allergic reaction. Coincidentally, pregabalin also has the potential to cause angioedema.

When taking pregabalin and ACE inhibitors together, there is an increased risk of angioedema. It’s important to be aware of the signs and symptoms of angioedema, including tongue or throat swelling, swelling around the eyes, a hot or painful sensation in the swollen areas, and difficulty breathing. If angioedema persists and affects the ability to breathe, this is a medical emergency and requires immediate attention. There are many different types of blood pressure medications that do not have the risk of causing angioedema that can be considered.

Examples of common ACE-Inhibitors include:

Other pregabalin interactions

In addition to interactions with other medications, there are other types of pregabalin interactions. Pregabalin can also interact with alcohol and cannabinoid-containing products.

Pregabalin and alcohol 

Alcohol is also a central nervous system depressant that slows down the nervous system. Drinking alcoholic beverages such as beer or cocktails can often cause an inability to react quickly, unsteady movement, slurred speech, disturbed perceptions, and impaired motor control. Side effects of pregabalin, when combined with alcohol, can be enhanced with even more nervous system depression that can lead to excessive sedation, an increased chance of falls, and a greater risk of accidental injury. People who drink alcohol should always check with their doctor or pharmacist if they can combine alcohol with their medications.


RELATED: 10 drugs you should not mix with alcohol

Pregabalin and CBD

Cannabinoid-containing (CBD) products can cause added effects on central nervous system depression. Various studies have shown that even short-term use of cannabis or tetrahydrocannabinol (THC, the primary known psychoactive component of cannabis) can enhance sedative, psychomotor, respiratory, and other side effects of CNS depressant drugs. While taking drugs like pregabalin, it’s best to avoid any cannabinoid-containing, illicit, unprescribed, or recreational CNS depressants.

RELATED: Are CBD products safe for people taking prescription medications?

How to minimize pregabalin interactions

Steps can be taken to help lessen the chance of pregabalin interactions. It’s important to keep healthcare providers updated on all medical conditions and ensure they have current medication lists, including prescription drugs, over-the-counter (OTC) medications, herbal products, and supplements. Even OTC and supplement products can have dangerous drug interactions. It’s also important to be honest with providers about alcohol and other substance use. Additionally, pharmacists are excellent resources and can provide medical advice and additional drug information when visiting the pharmacy.

Some medical conditions can help decide if a drug will be safe or not for a person. Pregabalin should be used with caution in people with kidney disease and will sometimes require dose adjustments. Pregabalin is present in breast milk, and the drug manufacturer does not recommend using pregabalin in breastfeeding women.

When to talk to a healthcare provider about pregabalin interactions

While many of the serious drug interactions are included above, several other pregabalin drug interactions are not included. Communicating openly with healthcare providers about all medications, supplements, and medical conditions is important to ensure proper drug management and monitoring. For some people, there are alternative medication options for treating their condition, such as epilepsy or neuropathic pain, that may be safer treatment options.