Hydrocodone is a schedule II semi-synthetic opioid medication used to treat pain.
It is available as Immediate-release (IR) hydrocodone as a combination product combined with acetaminophen, ibuprofen, and other drugs.
It is approved for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Single-entity hydrocodone is only available in extended-release (ER) formulations.
It is also an antitussive and indicated for cough in adults.
FDA requires safety labeling changes for prescription cough and cold medicines containing hydrocodone or codeine to limit the use of these products to adults 18 years of age and older.
It is an opioid receptor agonist and produces its analgesic effects by activating mu-opioid receptors.
It also activates delta-opioid receptors and kappa-opioid receptors as the plasma drug concentration increases beyond typical starting doses.
Opioid receptors are located: primarily in the CNS, enteric plexus of the bowel, interstitial cells of Cajal, and immune cells of the gastrointestinal tract.
Opioid receptors are G-protein-coupled receptors,
Opioid receptors agonist stimulation inhibits the formation of cyclic adenosine monophosphate (cAMP), leading to inhibition of the release of nociceptive neurotransmitters, post-synaptic neuronal hyperpolarization, and reduced neuronal excitability.
An oral medication with formulations, including tablets, capsules, and oral solutions.
Tablets and capsules are not to be crushed, chewed, or dissolved, as such activities can lead to uncontrolled rapid medication delivery and overdose.
Hydrocodone combination product dosages typically range from 2.5 mg to 10 mg every 4 to 6 hours as needed.
No dosage modification is required for patients with renal or hepatic dysfunction.
Hydrocodone ER formulations are available in both tablets and capsules, with the initial dosing between 10 mg to 20 mg every 12 hours to 24 hours.
The liver metabolizes hydrocodone in primarily via the cytochrome P450 enzymes CYP2D6 and CYP3A4.
Hydrocodone converts to its active metabolite, hydromorphone.
Hydrocodone conversion occurs by O-demethylation catalyzed by the CYP2D6 enzyme.
Pain relief correlates with plasma concentrations of hydromorphone rather than hydrocodone.
Hydrocodone is also metabolized to an inactive metabolite, norhydrocodone, by CYP3A4 enzyme.
Genetic polymorphisms in CYP2D6 metabolism can lead to variations in plasma hydrocodone concentrations in different people: ultra-rapid, extensive, and weak metabolizer phenotypes.
Hydrocodone immediate release and extended release drugs reach a maximum serum concentration within 1 hour and 5 to 30 hours, respectively.
The half-life elimination of hydrocodone immediate release and extended release is about 4 hours and 7 to 12 hours, respectively.
The excretion occurs via the urine.
Adverse effects: constipation and nausea (>10%).
Other adverse effects of hydrocodone include:
Respiratory depression, cough, shortness of breath
Cardiovascular: Hypotension, hypertension, peripheral edema
Neurologic: Headache, chills, anxiety, sedation, insomnia, dizziness, drowsiness, fatigue
Dermatologic: Pruritus, diaphoresis, rash
Gastrointestinal: Vomiting, diarrhea, dyspepsia, gastroenteritis, abdominal pain
Genitourinary: Urinary tract infection, urinary retention associated with prostatic hypertrophy
Contraindications to its use:
Hypersensitivity, respiratory depression,
known or suspected GI obstruction, including paralytic ileus, asthma,
Opioids cross the placenta, and prolonged use during pregnancy may cause neonatal withdrawal syndrome.
Use with other central nervous system depressants, such as alcohol, benzodiazepines, barbiturates, or other opioids, can lead to profound sedation and respiratory depression and should be avoided.
Medications that induce (rifampin, phenytoin, carbamazepine) or inhibit (cimetidine, fluoxetine, ritonavir) cytochrome enzymes should be used with caution and monitored, as this can lead to wide variations in hydrocodone plasma concentrations.
It has a potential interaction with warfarin that may lead to an elevated international normalized ratio (INR) and bleeding.
Toxicity signs and symptoms of hydrocodone: include difficulty breathing, apnea, bradycardia, miosis, clammy skin, cyanosis, hypotension, and loss of consciousness.
The opioid overdose is an opioid antagonist, such as naloxone.
Hydrocodone formulations with abuse-deterrent properties, can prevent abuse through chewing, injecting, or snorting.