Hydrocodone aspirin
   HOME

TheInfoList



OR:

Hydrocodone, also known as dihydrocodeinone, is an opioid used to treat
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
and as a
cough suppressant Cold medicines are a group of medicinal, medications taken individually or in Combination drug, combination as a Symptomatic treatment, treatment for the symptoms of the common cold and similar conditions of the upper respiratory tract. The t ...
. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe enough to require an opioid and in combination with
homatropine methylbromide Homatropine methylbromide (INN; also known as methylhomatropine bromide) is a quaternary ammonium salt of methylhomatropine. It is a peripherally acting anticholinergic medication that inhibits muscarinic acetylcholine receptors and thus the para ...
to relieve cough. It is also available by itself in a long-acting form under the brand name Zohydro ER, among others, to treat severe pain of a prolonged duration. Hydrocodone is a controlled drug, in the United States a Schedule II Controlled Substance. Common side effects include dizziness, sleepiness, nausea, and constipation. Serious side effects may include low blood pressure, seizures, QT prolongation,
respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...
, and serotonin syndrome. Rapidly decreasing the dose may result in opioid withdrawal. Use during pregnancy or breastfeeding is generally not recommended. Hydrocodone is believed to work by activating opioid receptors, mainly in the brain and spinal cord. Hydrocodone 10 mg is equivalent to about 10 mg of morphine by mouth. Hydrocodone was patented in 1923, while the long-acting formulation was approved for medical use in the United States in 2013. It is most commonly prescribed in the United States, which consumed 99% of the worldwide supply as of 2010. In 2018, it was the 402nd most commonly prescribed medication in the United States, with more than 400thousand prescriptions. Hydrocodone is a semisynthetic opioid, converted from
codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...
or less often from thebaine. Production using genetically engineered yeasts have been developed but are not used commercially.


Medical uses

Hydrocodone is used to treat moderate to severe pain. In liquid formulations, it is used to treat cough. In one study comparing the potency of hydrocodone to that of oxycodone, it was found that it took 50% more hydrocodone to achieve the same degree of miosis (pupillary contraction). The investigators interpreted this to mean that oxycodone is about 50% more potent than hydrocodone. However, in a study of
emergency department An emergency department (ED), also known as an accident and emergency department (A&E), emergency room (ER), emergency ward (EW) or casualty department, is a medical treatment facility specializing in emergency medicine, the acute care of pati ...
patients with fractures, it was found that an equal amount of either drug provided about the same degree of pain relief, indicating that there is little practical difference between them when used for that purpose. Some references state that the analgesic action of hydrocodone begins in 20–30 minutes and lasts about 4–8 hours. The manufacturer's information says onset of action is about 10–30 minutes and duration is about 4–6 hours. Recommended dosing interval is 4–6 hours.


Available forms

Hydrocodone is available in a variety of formulations for oral administration: * The original oral form of hydrocodone alone, Dicodid, as immediate-release 5- and 10-mg tablets is available for prescription in Continental Europe per national drug control and prescription laws and Title 76 of the Schengen Treaty, but dihydrocodeine has been more widely used for the same indications since the beginning in the early 1920s, with hydrocodone being regulated the same way as morphine in the German
Betäubungsmittelgesetz The Betäubungsmittelgesetz (BtMG), generally meaning Narcotics Law, is the controlled substances law of Germany. In common with the Misuse of Drugs Act of 1971 of the United Kingdom and Controlled Substances Acts of the US and Canada, it is a con ...
, the similarly named law in Switzerland and the Austrian Suchtmittelgesetz, whereas dihydrocodeine is regulated like
codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...
. For a number of decades, the liquid hydrocodone products available have been cough medicines. * Hydrocodone plus
homatropine Homatropine (Equipin, Isopto Homatropine) is an anticholinergic medication that is an antagonist at muscarinic acetylcholine receptors and thus the parasympathetic nervous system. It is used in eye drops as a cycloplegic (to temporarily paraly ...
(Hycodan) in the form of small tablets for coughing and especially neuropathic moderate pain (the homatropine, an anticholinergic, is useful in both of those cases and is a deterrent to intentional overdose) was more widely used than Dicodid and was labelled as a cough medicine in the United States whilst Vicodin and similar drugs were the choices for analgesia. * Extended-release hydrocodone in a time-release syrup also containing chlorphenamine/ chlorpheniramine is a cough medicine called Tussionex in North America. In Europe, similar time-release syrups containing codeine (numerous), dihydrocodeine (Paracodin Retard Hustensaft), nicocodeine (Tusscodin),
thebacon Thebacon (INN; pronounced ), or dihydrocodeinone enol acetate, is a semisynthetic opioid that is similar to hydrocodone and is most commonly synthesised from thebaine. Thebacon was invented in Germany in 1924, four years after the first synthe ...
,
acetyldihydrocodeine Acetyldihydrocodeine is an opiate derivative discovered in Germany in 1914 and was used as a cough suppressant and analgesic. It is not commonly used, but has activity similar to other opiates. Acetyldihydrocodeine is a very close relative deri ...
,
dionine Ethylmorphine (also known as codethyline, dionine, and ethyl morphine) is an opioid analgesic and antitussive. Side effects Adverse effects are similar to other opioids and include drowsiness, constipation, vertigo, nausea, vomiting, and respira ...
, and nicodicodeine are used instead. * Immediate-release hydrocodone with
paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
(acetaminophen) (Vicodin, Lortab, Lorcet, Maxidone, Norco, Zydone) * Immediate-release hydrocodone with
ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
(Vicoprofen, Ibudone, Reprexain) * Immediate-release hydrocodone with aspirin (Alor 5/500, Azdone, Damason-P, Lortab ASA, Panasal 5/500) * Controlled-release hydrocodone (Hysingla ER by Purdue Pharma, Zohydro ER) Hydrocodone is not available in
parenteral A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...
or any other non-oral forms.


Side effects

Common side effects of hydrocodone are nausea, vomiting, constipation, drowsiness, dizziness, lightheadedness, anxiety, abnormally happy or sad mood, dry throat, difficulty urinating, rash, itching, and contraction of the pupils. Serious side effects include slowed or irregular breathing and chest tightness.MedlinePlus; Drug Information: Hydrocodone.
Last Revised—1 October 2008. Retrieved on 20 April 2013.
Several cases of progressive bilateral hearing loss unresponsive to steroid therapy have been described as an infrequent adverse reaction to hydrocodone/paracetamol misuse. This adverse effect has been considered by some to be due to the ototoxicity of hydrocodone. Other researchers have suggested that paracetamol is the primary agent responsible for the ototoxicity. Hydrocodone is in U.S. Food and Drug Administration (FDA) pregnancy category C. No adequate and well-controlled studies in humans have been conducted. A newborn of a mother taking opioid medications regularly prior to the birth will be physically dependent. The baby may also exhibit respiratory depression if the opioid dose was high. An epidemiological study indicated that opioid treatment during early pregnancy results in increased risk of various birth defects. Symptoms of hydrocodone overdose include narrowed or widened pupils; slow, shallow, or stopped breathing; slowed or stopped heartbeat; cold, clammy, or blue skin; excessive sleepiness; loss of consciousness; seizures; or death. Hydrocodone can be habit forming, causing physical and psychological dependence. Its abuse liability is similar to morphine and less than oxycodone.


Interactions

Hydrocodone is
metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
by the
cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
enzymes CYP2D6 and
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
, and
inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...
s and inducers of these enzymes can modify hydrocodone exposure. One study found that combination of paroxetine, a selective serotonin reuptake inhibitor (SSRI) and strong CYP2D6 inhibitor, with once-daily extended-release hydrocodone, did not modify exposure to hydrocodone or the incidence of adverse effects. These findings suggest that hydrocodone can be coadministered with CYP2D6 inhibitors without dosage modification. Conversely, combination of
hydrocodone/acetaminophen Hydrocodone/paracetamol (also known as hydrocodone/acetaminophen) is the combination of the analgesic, pain medications hydrocodone and paracetamol (acetaminophen). It is used to treat moderate to severe pain. It is taken Oral administration, b ...
with the antiviral regimen of ombitasvir,
paritaprevir Paritaprevir (previously known as ABT-450) is an acylsulfonamide inhibitor of the NS3- 4A serine protease manufactured by Abbott Laboratories that shows promising results as a treatment of hepatitis C. When given in combination with ritonavir an ...
, ritonavir, and
dasabuvir Dasabuvir, sold under the brand name Exviera, is an antiviral medication for the treatment of hepatitis C. It is often used together with the combination medication ombitasvir/paritaprevir/ritonavir specifically for hepatitis C virus (HCV) type 1 ...
for treatment of
hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
increased
peak concentrations Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose. It is a standard measurement in pharm ...
of hydrocodone by 27%,
total exposure Total may refer to: Mathematics * Total, the summation of a set of numbers * Total order, a partial order without incomparable pairs * Total relation, which may also mean ** connected relation (a binary relation in which any two elements are compa ...
by 90%, and elimination half-life from 5.1hours to 8.0hours. Ritonavir is a strong CYP3A4 inhibitor as well as inducer of CYP3A and other enzymes, and the other antivirals are known to inhibit
drug transporter A membrane transport protein (or simply transporter) is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane ...
s like
organic anion transporting polypeptide Members of the Organo Anion Transporter (OAT) Family (organic-anion-transporting polypeptides, OATP) are membrane transport proteins or 'transporters' that mediate the transport of mainly organic anions across the cell membrane. Therefore, OATPs a ...
(OATP) 1B1 and 1B3,
P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
, and
breast cancer resistance protein ATP-binding cassette super-family G member 2 is a protein that in humans is encoded by the ''ABCG2'' gene. ABCG2 has also been designated as CDw338 ( cluster of differentiation w338). ABCG2 is a translocation protein used to actively pump drugs ...
(BCRP). The changes in hydrocodone levels are consistent with CYP3A4 inhibition by ritonavir. Based on these findings, a 50% lower dose of hydrocodone and closer clinical monitoring was recommended when hydrocodone is used in combination with this antiviral regimen. People consuming
alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...
, other opioids, anticholinergic antihistamines, antipsychotics, anxiolytics, or other central nervous system (CNS) depressants together with hydrocodone may exhibit an additive
CNS depression Central nervous system (CNS) depression is a physiological state that can result in a decreased rate of breathing, decreased heart rate, and loss of consciousness possibly leading to coma or death. It is the result of inhibited or suppressed brai ...
. Hydrocodone taken concomitantly with serotonergic medications like SSRI
antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
s may increase the risk of serotonin syndrome.


Pharmacology


Pharmacodynamics

Hydrocodone is a highly selective full agonist of the
μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical Π...
(MOR). This is the main biological target of the
endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...
opioid neuropeptide β-endorphin. Hydrocodone has low
affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...
for the
δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous ligan ...
(DOR) and the κ-opioid receptor (KOR), where it is an
agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
similarly. Studies have shown hydrocodone is stronger than
codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...
but only one-tenth as potent as morphine at binding to receptors and reported to be only 59% as potent as morphine in analgesic properties. However, in tests conducted on rhesus monkeys, the analgesic potency of hydrocodone was actually higher than morphine. Oral hydrocodone has a mean equivalent daily dosage (MEDD) factor of 0.4, meaning that 1 mg of hydrocodone is equivalent to 0.4 mg of intravenous morphine. However, because of morphine's low
oral bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100 ...
, there is a 1:1 correspondence between orally administered morphine and orally administered hydrocodone.


Pharmacokinetics


Absorption

Hydrocodone is only pharmaceutically available as an oral medication. It is well- absorbed, but the oral bioavailability of hydrocodone is only approximately 25%. The onset of action of hydrocodone via this route is 10 to 20 minutes, with a peak effect ( Tmax) occurring at 30 to 60 minutes, and it has a duration of 4 to 8 hours.


Distribution

The volume of distribution of hydrocodone is 3.3 to 4.7 L/kg. The plasma protein binding of hydrocodone is 20 to 50%.


Metabolism

In the liver, hydrocodone is transformed into several
metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s, including
norhydrocodone Norhydrocodone is the major metabolite of the opioid analgesic hydrocodone. It is formed from hydrocodone in the liver via N-demethylation predominantly by CYP3A4. Unlike hydromorphone, a minor metabolite of hydrocodone, norhydrocodone is describ ...
, hydromorphone, 6α-hydrocodol (dihydrocodeine), and 6β-hydrocodol. 6α- and 6β-hydromorphol are also formed, and the metabolites of hydrocodone are conjugated (via glucuronidation). Hydrocodone has a terminal half-life that averages 3.8 hours (range 3.3–4.4 hours). The hepatic
cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
enzyme CYP2D6 converts hydrocodone into hydromorphone, a more potent opioid (5-fold higher binding affinity to the MOR). However, extensive and poor
cytochrome 450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...
CYP2D6 metabolizers had similar physiological and subjective responses to hydrocodone, and CYP2D6 inhibitor quinidine did not change the responses of extensive metabolizers, suggesting that inhibition of CYP2D6 metabolism of hydrocodone has no practical importance. Ultra-rapid CYP2D6 metabolizers (1–2% of the population) may have an increased response to hydrocodone; however, hydrocodone metabolism in this population has not been studied. Norhydrocodone, the major metabolite of hydrocodone, is predominantly formed by CYP3A4-catalyzed oxidation. In contrast to hydromorphone, it is described as inactive. However, norhydrocodone is actually a MOR agonist with similar potency to hydrocodone, but has been found to produce only minimal analgesia when administered peripherally to animals (likely due to poor
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
and thus central nervous system penetration). Inhibition of CYP3A4 in a child who was, in addition, a poor CYP2D6 metabolizer, resulted in a fatal overdose of hydrocodone. Approximately 40% of hydrocodone metabolism is attributed to non-cytochrome P450-catalyzed reactions.


Elimination

Hydrocodone is
excreted Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...
in urine, mainly in the form of conjugates.


Chemistry


Detection in body fluids

Hydrocodone concentrations are measured in blood, plasma, and urine to seek evidence of misuse, to confirm diagnoses of poisoning, and to assist in investigations into deaths. Many commercial opiate screening tests react indiscriminately with hydrocodone, other opiates, and their metabolites, but chromatographic techniques can easily distinguish hydrocodone uniquely. Blood and plasma hydrocodone concentrations typically fall into the 5–30 Âµg/L range among people taking the drug therapeutically, 100–200 Âµg/L among recreational users, and 100–1,600 Âµg/L in cases of acute, fatal overdosage. Co-administration of the drug with food or alcohol can very significantly increase the resulting plasma hydrocodone concentrations that are subsequently achieved.


Synthesis

Hydrocodone is most commonly synthesized from Thebaine, a constituent of opium latex from the dried poppy plant. Once Thebaine is obtained, the reaction undergoes hydrogenation using a palladium catalyst.


Structure

There are three important structures in hydrocodone: the amine group, which binds to the tertiary nitrogen binding site in the central nervous system's opioid receptor, the
hydroxy group In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
that binds to the anionic binding side, and the
phenyl group In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...
which binds to the phenolic binding site. This triggers a G protein activation and subsequent release of
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
.


History

Hydrocodone was first synthesized in Germany in 1920 by
Carl Mannich Carl Ulrich Franz Mannich (8 March 1877 in Breslau – 5 March 1947 in Karlsruhe) was a German chemist. From 1927 to 1943 he was professor for pharmaceutical chemistry at the University of Berlin. His areas of expertise were keto bases, alcoh ...
and Helene Löwenheim. It was approved by the Food and Drug Administration on 23 March 1943 for sale in the United States and approved by
Health Canada Health Canada (HC; french: Santé Canada, SC)Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary unit ...
for sale in Canada under the brand name Hycodan. See section I. B., ''DESI Review of Hydrocodone Products'' Hydrocodone was first marketed by Knoll as Dicodid, starting in February 1924 in Germany. This name is analogous to other products the company introduced or otherwise marketed: Dilaudid (hydromorphone, 1926), Dinarkon (oxycodone, 1917), Dihydrin (dihydrocodeine, 1911), and Dimorphan (
dihydromorphine Dihydromorphine (Paramorfan, Paramorphan) is a semi-synthetic opioid structurally related to and derived from morphine. The 7,8-double bond in morphine is reduced to a single bond to get dihydromorphine.Rama Rao Nadendla. Principles Of Organic ...
). Paramorfan is the trade name of dihydromorphine from another manufacturer, as is Paracodin, for dihydrocodeine. The name Dicodid was registered in the United States and appears without a monograph as late as 1978 in the
Physicians' Desk Reference The ''Prescriber's Digital Reference'' (''PDR'') is a compilation of manufacturers' prescribing information (package insert) on prescription drugs, updated regularly and published by ConnectiveRx. History The original PDR was titled "Physician ...
; Dicodid may have been marketed to one extent or another in North America in the 1920s and early 1930s. The drug was pure hydrocodone in small 5 and 10 mg tablets, physically similar to the Dilaudid tablets. It is no longer manufactured by Knoll in Germany, nor is a generic available. Hydrocodone was never as common in Europe as it is in North America—dihydrocodeine is used for its spectrum of indications. Germany was the number two consumer of hydrocodone until the manufacture of the drug was discontinued there. Now, the world outside the United States accounts for less than 1% of annual consumption. It was listed as a ''Suchtgift'' under the German Betäubungsmittelgesetz and regulated like morphine. It became available in the
Schengen Area The Schengen Area ( , ) is an area comprising 27 European countries that have officially abolished all passport and all other types of border control at their mutual borders. Being an element within the wider area of freedom, security and j ...
of the European Union as of 1 January 2002 under Title 76 of the Schengen Treaty.


Society and culture


Formulations

Several common imprints for hydrocodone are M365, M366, M367.


Combination products

Most hydrocodone formulations include a second analgesic, such as paracetamol (acetaminophen) or ibuprofen. Examples of hydrocodone combinations include Norco, Vicodin, Vicoprofen and Riboxen.


Legal status


United States

The US government imposed tougher prescribing rules for hydrocodone in 2014, changing the drug from Schedule III to Schedule II. In 2011, hydrocodone products were involved in around 100,000 abuse-related emergency department visits in the United States, more than double the number in 2004.


References


External links

* * {{Portal bar , Medicine 4,5-Epoxymorphinans Euphoriants German inventions Ketones Mu-opioid receptor agonists Phenol ethers Semisynthetic opioids Wikipedia medicine articles ready to translate