Last reviewed by Miljan Krcobic on September 4th, 2018.
What is Hydrocodone
Hydrocodone is a Generic name for an opioid drug which is synthesized from codeine, an opioid alkaloid that can be found in the opium poppy.
This drug is narcotic analgesic which is used orally for relieving the moderate to severe pain, but it is also commonly used in liquid form as an antitussive agent for symptomatic relief of nonproductive cough, alone or together with other cough suppressants or expectorants.
This drug works by changing the way the brain and nervous system respond to pain. As an analgesic, hydrocodone is usually combined with ibuprofen, acetaminophen or aspirin for pain treatment.
The analgesic action of hydrocodone starts in 20–30 minutes and lasts for about 4–8 hours. However, hydrocodone is only used for the treatment of patients who are expected to need painkiller for severe pain for a long time, and who cannot be treated with other medicines or treatments.
Hydrocodone is predominantly prescribed in the US. According to the the International Narcotics Control Board, 99% of the worldwide hydrocone supply in 2007 was consumed in the US.
Other Brand names on the market containing hydrocodone are: Hysingla ER, Zohydro ER, Norco, Vicodin and Robidone.
What are Naproxen and Aleve
Aleve is a Brand name for a drug containing naproxen sodium as an active ingredient while Naproxen is a Generic name for the drug containing the same active ingredient.
They are nonsteroidal anti-inflammatory drug (NSAID) which are used as a pain relievers for various conditions such as: headaches, dental pain, muscle pain, tendinitis (inflammation or irritation of a tendon, a thick cord that attaches bone to muscle), menstrual cramps, and for the treatment of pain, swelling and joint stiffness caused by arthritis, osteoarthritis, juvenile arthritis, bursitis, ankylosing spondylitis and gout.
They can also be used to temporarily reduce fever and for the treatment of common cold. These drugs are available in the form of capsule and tablets in dose of 220mg of naproxen-sodium.
Aleve products on the market are: Aleve caplets, Aleve tablets, Aleve gelcaps, Aleve liquid gels, Aleve PM (contains naproxen-sodium 220 mg + diphenhydramine hydrochloride 25 mg), and Aleve-D (contains naproxen-sodium 220 mg + pseudoephedrine HCl 120 mg, extended-release).
Naproxen products on the market are: Naproxen capsule, Naproxen tablet, Naproxen All Day Relief for Pain, Naproxen Liquid Gels, Naproxen Caplets All Day Relief for Pain, Naproxen Menstrual Pain Relief and Naproxen Sodium (nsaid) Fever Reducer / Pain Reliever.
Other Brand names for medications containing naproxen are: Anaprox, EC-Naprosyn, Flanax Pain Reliever, Leader Naproxen Sodium, Midol Extended Relief, Naprelan 375, Naprosyn.
How does Hydrocodone and Naproxen work in the body
Hydrocodone is an opioid agonist of opioid receptors within the CNS. This morphinans structure substance blocks pain perception in the cerebral cortex of the brain.
Hydrocodone decreases synaptic chemical transmission in the CNS, which in turn inhibits pain sensation into the higher centers of the brain. Agonist activities at the μ and kappa receptors can cause analgesia, miosis, and decreased body temperature.
Agonist activity at the μ receptor can also cause the suppression of opiate withdrawal, while antagonist activity can result in precipitation of withdrawal.
Hydrocodone acts at several locations within the CNS by involving several systems of neurotransmitters to produce analgesia, but the precise mechanism of action has not been fully understood.
Opiate agonists don’t change the threshold or responsiveness of afferent nerve endings to noxious stimuli nor the conduction of impulses along peripheral nerves.
Instead, they alter the perception of pain at the spinal cord and higher concentrations in the CNS and the person’s emotional response to pain.
Hydrocodone can produce inhibition at the chemoreceptors through μ-opioid receptors and in the medulla through μ and δ receptors which can lead to dose-related respiratory depression.
Naproxen inhibits synthesis of prostaglandins (substances in the body that play a key role in pain and inflammation processes in body tissues) by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2.
Inhibition of COX-2 leads to the anti-inflammatory, analgesic and antipyretic effects while the inhibition of COX-1 may cause gastrointestinal bleeding and ulcers.
COX-1-dependent prostaglandins play a crucial homeostatic role in physiological functions (gastrointestinal cytoprotection, aggregation of platelets and modulation of vascular muscle tone) while COX-2-dependent prostaglandins play dominant roles in pathophysiologic processes (inflammation and cancer, or physiological processes such as endothelial vasoprotection).
If NSAID drug less inhibits the COX-1, less side effect would be caused. Studies showed that naproxen has a lowest risk of provoking heart attack compared to all other NSAIDs.
This drug may also inhibit chemotaxis, decrease proinflammatory cytokine activity, alter lymphocyte activity, and inhibit neutrophil aggregation – these effects may also contribute to anti-inflammatory activity.
Can patients take Hydrocodone and Naproxen or Aleve together
From a pharmacology standpoint, there is no harm if Naproxen or Aleve is taken together with Hydrocodone. So if hydrocodone isn’t controlling the pain well, patients can use Naproxen or Aleve and Hydrocodone but only with physician instructions.
Naproxen is a blood thinner and may cause bleeding in predisposed patients, so if patient is already taking Hydrocodone for the treatment of post-surgical pain, in that case, these drugs shouldn’t be used together.
There are also many other factors that can exclude the usage of Naproxen and Hydrocodone combination such as: age, past medical history, pregnancy and breast-feeding, and possible interactions with other medications, food or alcohol.
However, Naproxen is the safest NSAID for the patients with coronary disease. It has the lowest risk of provoking heart attack.
Patients should avoid Aleve products containing antihistamines such as Aleve PM in combination with Hydrocodone. Antihistamines and Hydrocodone used together can increase the risk of side effects such as drowsiness and difficulties with concentration.
The table below shows side effects after Hydrocodone and Naproxen or Advil administration in recommendable doses. The incidence can be significantly increased if these drugs are overdosed or taken together.
|Very common side effects 10 – 40%||Constipation|
|Common and rare side effects 1-10%||Abdominal pain, Heartburn, Nausea, Vomiting, Edema, Dizziness, Drowsiness, Vertigo, Nausea, Headache, Somnolence Vomiting, Agitation, Emotional lability, Anxiety, Hallucinations, Euphoria, Nervousness, Asthenia, Pruritus, Dyspepsia, Spasticity, Diarrhea, Sweating, Dry mouth, Hypertonia, Malaise, Rash, Menopausal symptoms, Urinary frequency, Urinary retention, Visual disturbance, Vasodilation, Gastrointestinal bleeding, Perforation, and Ulcers, Dyspnea|
Special precautions and warnings during Hydrocodone and Naproxen or Aleve administration:
- Patients should tell their doctor and pharmacist if they are allergic to hydrocodone or naproxen, or any other medicines, or any of the ingredients that are used in Hydrocodone or Aleve or Naproxen products.
- Patients should tell their doctors or pharmacists what prescription and nonprescription medicines, vitamins or nutritional supplements they are taking or plan to take.
- Patients should also tell their doctors if they are using any of the following medications: antihistamines; dronedarone, medications for irritable bowel disease, Parkinson’s disease and ulcers, haloperidol, azithromycin, amiodarone, butorphanol;chlorpromazine; citalopram, laxatives such as lactulose, nalbuphine; or pentazocine, levofloxacin.
- They should also tell their doctors if they are taking the following medications or have stopped taking them within the past two weeks: isocarboxazid (Marplan), selegiline (Eldepryl, Emsam, Zelapar), phenelzine (Nardil), rasagiline (Azilect), or tranylcypromine (Parnate). Doctor may need to change the doses of medicines or monitor carefully for side effects.
- Hydrocodone shouldn’t be used if patient has blockage of stomach or intestines, or paralytic ileus.
- Patients should tell their doctor if they have or have ever had hypotension, difficulties with urinating, seizure attacks, or any of the thyroid, liver, kidney, gall bladder or pancreas disease.
- If patients are taking hydrocodone extended-release tablets, they should tell their doctor if they have or have ever had difficulties with swallowing, colon cancer, esophageal cancer, heart failure or heart rhythm problems such long QT syndrome.
- Patients should tell their doctor if they are breastfeeding.
- If patients are having surgery, including dental surgery, they should tell their doctor or dentist that they are taking hydrocodone.
- Hydrocodone may make patients drowsy. Patients taking hydrocodone should not drive a car or operate machinery.
- Hydrocodone may cause dizziness, fainting and lightheadedness, if patient get up too quickly from a lying position. This is more common when initial dose of hydrocodone is taken. To avoid this problem, patients should slowly get out of bed, resting their feet on the floor for a few minutes before standing up.
- Hydrocodone can cause constipation. Patients should talk with their doctor about changing diet and using other medications to treat or prevent constipation.
- There aren’t also appropriate studies on the relationship of geriatric-specific problems with the effects of naproxen and hydrocodone combination. However, elderly patients are more likely to develop kidney or stomach problems which are age-related. Hydrocodone is more likely to cause breathing problems in older patients who are severely ill, malnourished, or if they have other risk factors
- Pregnant patients should never use these medicines; because their babies could become drug dependent, so life-threatening withdrawal symptoms can be caused after baby is born. Those babies may need medical treatment for several weeks. Patients should tell doctor if they are pregnant or plan to become pregnant
- If patient should have surgery, including dental surgery, he/she should tell the doctor or dentist that he/she is taking naproxen
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