Published on 06 October 2022

Should You Take Tramadol And Zolpidem Together?

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We must have learned that some medicines are highly effective when taken alone and work differently when combined. Insomnia is a sleep disorder affecting up to 70 million Americans annually. While overall, findings indicate that more than 1 in 5 adults in America experiences chronic pain. In this blog, we shall discuss the effect of two common drugs when taken together.

Zolpidem (Ambien) is a sedative, also called a hypnotic, used to treat insomnia. At the same time, Tramadol is a strong painkiller from a group of medicines called opiates or narcotics. It is used to treat moderate-to-severe pain. 

Continue reading to learn about Tramadol and zolpidem for more information.

Tramadol And Its Uses

Tramadol is a centrally-acting analgesic to relieve moderate to severe pain. Tramadol is available as drops, sustained-release formulations, capsules for oral use, suppositories for rectal use, and intravenous, intramuscular, and subcutaneous injections. 

Depending on the patient's response and intensity of pain, prescribers modify the tramadol dosage; 50 to 100 mg four times per day typically suffices to relieve moderate to severe pain. FDA designated Tramadol as a controlled substance in 2014 because of the potential for abuse.

  • Effective in moderate to severe pain in adults when other therapies are inadequate, including rheumatological and neuropathic pain.
  • Relieves post-operative pain.
  • Useful in patients at risk for impaired cardiopulmonary function following thoracic or upper abdominal surgery and in situations when non-opioid analgesics are contraindicated
  • Used in the therapy of chronic pain of malignant or nonmalignant origin, notably neuropathic pain
  • Relieves pain caused by trauma, renal or biliary colic, labor, and other conditions.

Zolpidem And Its Uses

Zolpidem is used for the short-term treatment of insomnia in adults who have difficulty falling and staying asleep. It is well-known for low tolerance and starts working within 15 minutes. 

Zolpidem has a short half-life of two to three hours. It lessens the lingering hangover effects of nighttime medication, such as tiredness and reduced psychomotor and cognitive function, which may persist throughout the next day. Zolpidem comes in immediate-release, extended-release, and sublingual tablets and oral spray.

  • used to treat insomnia and some neurological conditions
  • relieves migraine headaches and stress

How Does Tramadol Work?

Tramadol is a member of the opioid agonist drug class. It is a unique, dual-action, centrally-acting analgesic that inhibits neurotransmitter reuptake and exerts agonistic characteristics at opioid receptors.

Tramadol blocks the transmission of pain signals to the brain by inhibiting the reuptake of norepinephrine and serotonin and weakly binding to μ-opioid receptors.

The mechanism of Tramadol can cause sleepiness, which is one of its most prevalent adverse effects, affecting 16% to 25% of individuals in clinical trials. Tramadol can also cause dizziness or lightheadedness. Do not drive, operate heavy machinery, or engage in risky activities until you understand how this medicine affects you.

How Does Zolpidem Work?

Zolpidem is an imidazopyridine that binds preferentially to GABA (A) receptors with the α1 subunit and slows brain activity. It enhances the inhibitory effects of GABA on neuronal excitation and induces sleep.

The action includes reducing sleep latency and increasing sleep duration in patients with insomnia. It has a rapid onset of effort and a half-life of 2-3 hours.

Frequently Asked Questions

If you misuse zolpidem and Tramadol, it can make you high and make you feel relaxed.
Zolpidem is a short-term drug for sleep disorders such as insomnia. Weight gain or weight loss is its typical side effect. During the withdrawal of zolpidem, a decrease in body weight, relative food intake, and anxiety can be observed, but you need to consult your doctor if these symptoms persist.
The consumption of Tramadol and zolpidem can lead to serious side effects, including respiratory disorder, coma, and even death.

Can You Take Zolpidem And Tramadol At The Same Time?

It is not advised to combine Tramadol with Zolpidem. The possible side effects of taking zolpidem and Tramadol include respiratory problems, coma, and even death.

Under certain circumstances, taking zolpidem and Tramadol together may be necessary. Your doctor may adjust the dosage or frequency of taking your medication. The enzyme cytochrome P450 3A4 metabolizes both Tramadol and zolpidem. As a result, competitive inhibition may increase the toxicity of the drug.

The phase IV clinical study analyzes the interactions with administering Zolpidem and Tramadol in combination. The administration of these two medicines can cause urinary tract infections among females and chronic kidney disease among males.

This data is concluded based on reports of 5,850 people who administer Zolpidem and Tramadol from the FDA. This data is updated regularly and can be used as a reference while recommending a suitable treatment.

What Happens When You Take Zolpidem And Tramadol Together?

  • Patients who take Tramadol and Zolpidem have reported drug interactions. Urinary tract infections in women and chronic renal disease in men are frequent interactions.
  • When Tramadol or zolpidem are taken acutely in large doses, QT prolongation is an established drug interaction.
  • The phase IV clinical study analyzes drug interactions of people taking Zolpidem and Tramadol. According to eHealthMe, based on reports from the FDA, 5,850 people take Zolpidem and Tramadol.
  • Tramadol and zolpidem taken immediately in large doses may result in QT prolongation. 
  • Tramadol and zolpidem blood concentrations that are toxic and lethal have been documented in post-mortem cases.
  • A study by Lee reported a case of acute intoxication by Tramadol and zolpidem, resulting in QT prolongation in a patient in whom serial blood and urine tramadol and zolpidem concentrations were determined. 

Possible Side Effects Of Tramadol And Zolpidem










nausea and vomiting

dry mouth


chest pain

lack of energy




dry mouth



muscle pain


trouble breathing


swelling of your tongue or face

slowed breathing rate

lack of energy




Standard Reports Of Reactions Of Taking Zolpidem And Tramadol Together

  • Abdominal pain: 121 reports
  • Anxiety and stress: 217 reports
  • Arrhythmia: 48 reports
  • Arthralgia (joint pain): 145 reports
  • Bradycardia (abnormally slow heart action): 50 reports
  • Chest pain: 93 reports
  • Constipation: 94 reports
  • Cough: 59 reports
  • Death: 182 reports
  • Depression: 174 reports
  • Diarrhea: 171 reports
  • Drowsiness: 100 reports
  • Fatigue: 230 reports
  • Hair loss: 70 reports
  • Headaches: 162 reports
  • Heart attack: 50 reports
  • Hot flashes: 24 reports
  • Irritability: 37 reports
  • Itching: 68 reports
  • Lightheadedness: 142 reports
  • Loss of consciousness: 89 reports
  • Myalgia: 93 reports
  • Myocardial infarction: 50 reports
  • Nausea and vomiting: 210 reports
  • Overdose: 128 reports
  • Pneumonia: 188 reports
  • Reduced appetite: 118 reports
  • Ringing in the ears: 48 reports
  • Rubor (a response of body tissues to injury or irritation; characterized by pain, swelling, redness, and heat.
  • inflammation, redness): 103 reports
  • Shortness of breath: 201 reports
  • Sinus infection: 57 reports
  • Skin rash: 103 reports
  • Sleepiness - during the day: 100 reports
  • Somnolence (a state of near-sleep, a strong desire for sleep): 100 reports
  • Suicidal thoughts: 49 reports
  • Sweating - excessive: 93 reports
  • Urinary tract infection: 131 reports
  • Vertigo: 142 reports
  • Weight gain: 74 reports
  • Weight loss - 120 reports 

Precautions For Taking Zolpidem

Some precautions should be taken before taking any drug that can help reduce your chances of side effects from the medicines. Before taking zolpidem,

  • Inform the concerned doctor or medical practitioner if you are allergic to zolpidem or any other drug.
  • Tell your doctor about your medical history or family history of substance abuse, breathing problem, sleepwalking, or myasthenia gravis.
  • Before surgery, tell your doctor about all your products, including prescription, non-prescription, and herbal products.
  • Avoid or limit the use of alcoholic beverages while on this medication. Speak to your doctor if you are taking marijuana (cannabis).
  • Do not drive, use machinery, or perform any activity that requires alertness for at least 8 hours after taking this drug until you can do it safely. 
  • If you do not sleep 7 to 8 hours or consume other medications that make you sleepy, you may experience dizziness or blurred/double vision. 
  • Children and older adults might be more sensitive to the adverse effects of this drug, especially dizziness, confusion, excessive drowsiness, unsteadiness, and hallucinations. 
  • This medication should be administered during pregnancy or breastfeeding only when needed. Consult your doctor if you are pregnant or planning to conceive. Discuss the associated risks with the concerned healthcare professional if you experience any unusual effects in the newborn.

Following the directions on the medicine label or instructions from your doctor, pharmacist, or nurse is recommended.

Drug Interactions

The drugs that may interact with Tramadol and zolpidem include the following-

  • Antifungal drugs (such as ketoconazole)
  • CYP3A4 Inhibitor (such as rifampin, carbamazepine, ritonavir)
  • Benzodiazepines (such as alprazolam, xanax)
  • Phenytoin
  • Antipsychotics (such as clozapine and risperidone)
  • Opioids (such as codeine)
  • TCAs (such as amitriptyline, clomipramine)
  • SNRIs (such as duloxetine and venlafaxine)
  • Muscle relaxants (such as metaxalone, cyclobenzaprine)
  • MAOIs (such as Tranylcypromine, Buprenorphine)
  • Diuretics (such as atropine, spironolactone)
  • Anticholinergic drugs (such as dicyclomine, and clidinium)
  • Alcohol
  • Cannabis
  •  Antihistamines (such as cetrizine, diphenhydramine)

Please note that the list above might not be complete, and other interactions with drugs not listed here may occur.

Bottom Line From Practical Anxiety Solutions

Combining non-benzodiazepines that produce central nervous system depression with narcotic pain relievers or cough suppressants can have dangerous side effects, including respiratory difficulty, coma, and even death. Before using the drugs, if you have any questions or concerns, consult your doctor.

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  • Liappas IA, Malitas PN, Dimopoulos NP, Gitsa OE, Liappas AI, Nikolaou ChK, Christodoulou GN. Zolpidem dependence case series: possible neurobiological mechanisms and clinical management. J Psychopharmacol. 2003 Mar;17(1):131-5. doi: 10.1177/0269881103017001723. PMID: 12680751. Obtain on 06/10/2022
  • Grond, S., Sablotzki, A. Clinical Pharmacology of Tramadol. Clin Pharmacokinet 43, 879–923 (2004). Obtain on 06/10/2022