Dextropropoxyphene

Last updated
Dextropropoxyphene
Dextropropoxyphene structure.svg
Dextropropoxyphene3DanJ.gif
Clinical data
Trade names Darvon
AHFS/Drugs.com Monograph
MedlinePlus a682325
License data
Pregnancy
category
  • AU:C
Addiction
liability 		Low [1] [ failed verification ]
Routes of
administration 		By mouth, IV, rectal
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 40% [3]
Protein binding 78% [3]
Metabolism Liver-mediated, CYP3A4-mediated N-demethylation (major), aromatic hydroxylation (minor) and ester hydrolysis (minor) [3]
Elimination half-life 6–12 hours; 30–36 hours (active metabolite, nordextropropoxyphene) [4]
Excretion Urine (major), breastmilk (minor) [3]
Identifiers
  • (1S,2R)-1-benzyl-3-(dimethylamino)-2-methyl-1-phenylpropyl propionate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.006.747 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H29NO2
Molar mass 339.479 g·mol−1
3D model (JSmol)
Melting point 75 °C (167 °F)
  • CCC(=O)O[C@](Cc1ccccc1)(c2ccccc2)[C@H](C)CN(C)C
  • InChI=1S/C22H29NO2/c1-5-21(24)25-22(18(2)17-23(3)4,20-14-10-7-11-15-20)16-19-12-8-6-9-13-19/h6-15,18H,5,16-17H2,1-4H3/t18-,22+/m1/s1 Yes check.svgY
  • Key:XLMALTXPSGQGBX-GCJKJVERSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Dextropropoxyphene [5] is an analgesic in the opioid category, patented in 1955 [6] and manufactured by Eli Lilly and Company. It is an optical isomer of levopropoxyphene. It is intended to treat mild pain and also has antitussive (cough suppressant) and local anaesthetic effects. The drug has been taken off the market in Europe and the US due to concerns of fatal overdoses and heart arrhythmias. [7] It is still available in Australia, albeit with restrictions after an application by its manufacturer to review its proposed banning. [8] Its onset of analgesia (pain relief) is said to be 20–30 minutes and peak effects are seen about 1.5–2.0 hours after oral administration. [3]

Contents

Dextropropoxyphene is sometimes combined with acetaminophen. Trade names include Darvocet-N, Di-Gesic, [9] and Darvon with APAP (for dextropropoxyphene and paracetamol). [10] The British approved name (i.e. the generic name of the active ingredient) of the paracetamol/dextropropoxyphene preparation is co-proxamol (sold under a variety of brand names); however, it has been withdrawn since 2007, and is no longer available to new patients, with exceptions. [11] The paracetamol combination(s) are known as Capadex or Di-Gesic in Australia, Lentogesic in South Africa, and Di-Antalvic in France (unlike co-proxamol, which is an approved name, these are all brand names).

Dextropropoxyphene is known under several synonyms, including:

Uses

Analgesia

Dextropropoxyphene is generally considered a weak analgesic, with several studies finding its efficacy is no better than acetaminophen. [12] Like codeine, it is a weak opioid. However, dextropropoxyphene has one-third to one-half of the analgesic activity of codeine. [12]

Restless legs syndrome

Dextropropoxyphene has been found to be helpful in relieving the symptoms of restless legs syndrome. [13] [14] [15]

Contraindications

Dextropropoxyphene is contraindicated in patients allergic to paracetamol (acetaminophen) or dextropropoxyphene, and in alcoholics. It is not intended for use in patients who are prone to suicide, anxiety, panic, or addiction.

Side effects

Severe toxicity can occur with small increments above the therapeutic dose including cardiotoxicity, and fatal overdoses. This is especially true when the drug is combined with alcohol. [16] Other side effects include: [17]

Propoxyphene.jpg
Propoxyphene2.jpg

Pharmacology

Dextropropoxyphene acts as a mu-opioid receptor agonist. It also acts as a potent, noncompetitive α3β4 neuronal nicotinic acetylcholine receptor antagonist, [18] as well as a weak serotonin reuptake inhibitor.

Toxicity

Overdose is commonly broken into two categories - liver toxicity (from paracetamol poisoning) and dextropropoxyphene overdose.

An overdose of dextropropoxyphene may lead to various systemic effects. Excessive opioid receptor stimulation is responsible for the CNS depression, respiratory depression, aspiration pneumonia, miosis, and gastrointestinal effects seen in propoxyphene poisoning. It may also account for mood- or thought-altering effects. In the presence of amphetamine, propoxyphene overdose increases CNS stimulation and may cause fatal convulsive seizures. [19]

In addition, both propoxyphene and its metabolite norpropoxyphene have local anesthetic effects at concentrations about 10 times those necessary for opioid effects. Norpropoxyphene is a more potent local anesthetic than propoxyphene, and they are both more potent than lidocaine. [20] Local anesthetic activity appears to be responsible for the arrhythmias and cardiovascular depression seen in propoxyphene poisoning. [21]

Both propoxyphene and norpropoxyphene are potent blockers of cardiac membrane sodium channels, and are more potent than lidocaine, quinidine, and procainamide in this respect. [22] As a result, propoxyphene and norpropoxyphene appear to have the characteristics of a Vaughn-Williams Class Ic antiarrhythmic.

These direct cardiac effects include decreased heart rate (i.e. cardiovascular depression), decreased contractility, and decreased electrical conductivity (i.e., increased PR, AH, HV, and QRS intervals). These effects appear to be due to their local anesthetic activity and are not reversed by naloxone. [20] [21] [23] Widening of the QRS complex appears to be a result of a quinidine-like effect of propoxyphene, and sodium bicarbonate therapy appears to have a positive direct effect on the QRS dysrhythmia. [24]

Seizures may result from either opioid or local anesthetic effects. [20] Pulmonary edema may result from direct pulmonary toxicity, neurogenic/anoxic effects, or cardiovascular depression. [21]

Balance disorder is possible, with risk of falls from standing height.

Available forms

Propoxyphene was initially introduced as propoxyphene hydrochloride. Shortly before the patent on propoxyphene expired, propoxyphene napsylate form was introduced to the market. Napsylate salt (the salt of naphthalenesulfonic acid) is claimed to be less prone to non-medical use, because it is almost insoluble in water, so cannot be used for injection. Napsylate also gives lower peak blood level. [25] Because of different molar mass, a dose of 100 mg of propoxyphene napsylate is required to supply an amount of propoxyphene equivalent to that present in 65 mg of propoxyphene hydrochloride.

Before the FDA-directed recall, dextropropoxyphene HCl was available in the United States as a prescription formulation with paracetamol (acetaminophen) in ratio from 30 mg / 600 mg to 100 mg / 650 mg (or 100 mg / 325 mg in the case of Balacet), respectively. These are usually named Darvocet. Darvon is a pure propoxyphene preparation that does not contain paracetamol.

In Australia, dextropropoxyphene is available on prescription, both as a combined product (32.5 mg dextropropoxyphene per 325 mg paracetamol branded as Di-gesic, Capadex, or Paradex; it is also available in pure form (100 mg capsules) known as Doloxene, however its use has been restricted. [8]

Drug testing

Detectable levels of propoxyphene/dextropropoxyphene may stay in a person's system for up to 9 days after last dose and can be tested for specifically in nonstandard urinalysis, but may remain in the body longer in minuscule amounts. [26] Propoxyphene does not show up on standard opiate/opioid tests because it is not chemically related to opiates as part of the OPI or OPI 2000 panels, which detect morphine and related compounds. It is most closely related to methadone. [27]

History

Dextropropoxyphene was successfully tested in 1954 as part of US Navy and CIA-funded research on nonaddictive substitutes for codeine. [28]

Use in organic synthesis

Without the propionyl group on the oxygen, the non-esterified alcohol precursor of propoxyphene (both enantiomers, known as darvon alcohol and novrad alcohol) have been employed as stoichiometric chiral reagents for asymmetric carbonyl reduction reactions involving aluminium hydride reagents. [29] [30]

Usage controversy and regulation

Dextropropoxyphene is subject to some controversy; while many physicians prescribe it for a wide range of mildly to moderately painful symptoms, as well as for treatment of diarrhea, many others refuse to prescribe it, citing limited effectiveness. In addition, the therapeutic index of dextroproxyphene is relatively narrow.

Caution should be used when administering dextropropoxyphene, particularly with children and the elderly and with patients who may be pregnant or breastfeeding; other reported problems include kidney, liver, or respiratory disorders, and prolonged use. Attention should be paid to concomitant use with tranquillizers, antidepressants, or excess alcohol.

Darvon, a dextropropoxyphene formulation made by Eli Lilly, which had been on the market for 25 years, came under heavy fire in 1978 by consumer groups that said it was associated with suicide. Darvon was never withdrawn from the market, until recently, but Lilly has waged a sweeping, and largely successful, campaign[ citation needed ] among doctors, pharmacists, and Darvon users to defend the drug as safe when it is used in proper doses and not mixed with alcohol. After determining the risks outweigh the benefits, the USFDA requested physicians stop prescribing the drug. On November 19, 2010, the FDA announced that Xanodyne Pharmaceuticals agreed to withdraw Darvon and Darvocet in the United States, followed by manufacturers of dextropropoxyphene. [31] [32]

Australia

In Australia, both pure dextropropoxyphene capsules (as napsylate, 100 mg), marketed as Doloxene, and combination tablets and capsules (with paracetamol) all containing 32.5 mg dextropropoxyphene HCl with 325 mg paracetamol, which are currently available on prescription were supposed to be withdrawn from 1 March 2012, [33] but Aspen Pharma sought a review in the Administrative Appeals Tribunal which ruled in 2013 that the drugs could be sold under strict conditions. [8]

Canada

On December 1, 2010, Health Canada and Paladin Labs Inc. announced the voluntary recall and withdrawal of Darvon-N from the Canadian market and the discontinuation of sale of Darvon-N. [34]

European Union

In November 2007, the European Commission requested the European Medicines Agency (EMA) to review the safety and effectiveness of dextropropoxyphene based medicines and on 25 June 2009 the EMA recommended a gradual withdrawal throughout the European Union. The EMA's conclusion was based on evidence that dextropropoxyphene-containing medicines were weak painkillers, the combination of dextropropoxyphene and paracetamol was no more effective than paracetamol on its own, and the difference between the dose needed for treatment and a harmful dose (the "therapeutic index") was too small. [35]

New Zealand

In February 2010, Medsafe announced Paradex and Capadex (forms of dextropropoxyphene) were being withdrawn from the marketplace due to health issues, and withdrawal in other countries. [36]

India

On June 12, 2013, the Indian government suspended the manufacture, sale, and distribution of the drug under Section 26A of the 1940 Drugs and Cosmetic Act. [37]

Sweden

In Sweden, physicians had long been discouraged by the medical products agency to prescribe dextropropoxyphene due to the risk of respiratory depression and even death when taken with alcohol. [38] Physicians had earlier been recommended to prescribe products with only dextropropoxyphene and not to patients with a history of substance use disorder, depression, or suicidal tendencies. Products with mixed active ingredients were taken off the market and only products with dextropropoxyphene were allowed to be sold. Dextropoxyphene was de facto narcotica labelled.

As of March 2011, all products containing the substance are withdrawn because of safety issues after a European Commission decision. [39] [40]

At the time, people who drank excessive amounts of alcohol and other substances and take combination dextropoxyphene / acetaminophen (paracetamol) were discussed as needing to take many combination tablets to reach euphoria, because the amount of dextropropoxyphene per tablet is relatively low (30–40 mg). The ingested paracetamol—the other component—may then reach liver toxic levels. In the case of alcoholics, who often already have damaged livers, even a relatively small overdose with paracetamol may produce hepatotoxicity, liver failure, and necrosis. This toxicity with the combination of overdosed dextroproxyphene (with its CNS/respiratory depression/vomit with risk for aspiration pneumonia, as well as cardiotoxicity) and paracetamol-induced liver damage can result in death.

United Kingdom

In the United Kingdom, preparations containing only dextropropoxyphene were discontinued in 2004. [41] In 2007, the Medicines and Healthcare products Regulatory Agency removed the licence for co-proxamol, also called distalgesic. [42] From then on in the UK, co-proxamol is only available on a named patient basis, for long-term chronic pain and only to those who have already been prescribed this medicine. Its withdrawal from the UK market is a result of concerns relating to its toxicity in overdose (even small overdoses can be fatal), and dangerous reaction with alcohol. Recreational use in the UK is uncommon. Many patients have been prescribed alternative combinations of drugs as a replacement. [11]

The motivation for the withdrawal of co-proxamol was the reduction in suicides and a key part of the agency's justification of its decision was based upon studies showing co-proxamol was no more effective than paracetamol alone in pain management. [43] [44]

The co-proxamol preparations available in the UK contained a subtherapeutic dose of paracetamol, 325 mg per tablet. [45] Patients were warned not to take more than eight tablets in one day, a total dose of 2600 mg paracetamol per day. Despite this reduced level, patients were still at a high risk of overdose; coproxamol was second only to tricyclic antidepressants as the most common prescription drugs used in overdose. [43] Following the reduction in prescribing in 2005–2007, prior to its complete withdrawal, the number of deaths associated with the drug dropped significantly. Additionally, patients have not substituted other drugs as a method of overdose. [46]

The decision to withdraw co-proxamol has met with some controversy; it has been brought up in the House of Commons on two occasions, 13 July 2005 [47] and on 17 January 2007. [48] Patients have found alternatives to co-proxamol either too strong, too weak, or with intolerable side effects.[ citation needed ] During the House of Commons debates, it is quoted that originally some 1,700,000 patients in the UK were prescribed co-proxamol. Following the phased withdrawal, this has eventually been reduced to 70,000. However, this apparently is the residual pool of patients who cannot find alternate analgesia to co-proxamol.[ citation needed ]

The safety net of prescribing co-proxamol after license withdrawal from 31 December 2007, on a "named patient" basis where doctors agree a clinical need exists, has been rejected by most UK doctors[ citation needed ] because the wording that "responsibility will fall on the prescriber" is unacceptable to most doctors. Some patients intend to take the case to the European Court of Human Rights. [49] However, the European Medicines Agency has recently backed the agency's decision, and recommended in June 2009 that propoxyphene preparations be withdrawn across the European Union. [50]

On 28 March 2017, NHS Clinical Commissioners announced that co-proxamol will be no longer available under NHS England as part of £400m of spending cuts for prescriptions that are believed to have little or no clinical value. [51]

United States

In January 2009, an FDA advisory committee voted 14 to 12 against the continued marketing of propoxyphene products, based on its weak pain-killing abilities, addictiveness, association with drug deaths and possible heart problems, including arrhythmia. A subsequent re-evaluation resulted in a July 2009 recommendation to strengthen the boxed warning for propoxyphene to reflect the risk of overdose. [52] Dextropropoxyphene subsequently carried a black box warning in the U.S., stating:

Propoxyphene should be used with extreme caution, if at all, in patients who have a history of substance/drug/alcohol abuse, depression with suicidal tendency, or who already take medications that cause drowsiness (e.g., antidepressants, muscle relaxants, pain relievers, sedatives, tranquilizers). Fatalities have occurred in such patients when propoxyphene was misused. [53]

Because of potential for side effects, this drug is on the list for high-risk medications in the elderly. [54]

On November 19, 2010, the FDA requested manufacturers withdraw propoxyphene from the US market, citing heart arrhythmia in patients who took the drug at typical doses. [55] Tramadol, which lacks the cardiotoxicity, has been recommended instead of propoxyphene, as it is also indicated for mild to moderate pain, and is less likely to be misused or cause addiction than other opioids. [56]

In the Stephen King short story collection Night Shift , the final story of the book, "The Woman in the Room", tells a tale in which the main character contemplates and then finally performs a mercy killing using a drug called "Darvon Complex."

Use by right-to-die societies

High toxicity and relatively easy availability made propoxyphene a drug of choice for right-to-die societies. It is listed in Dr. Philip Nitschke's The Peaceful Pill Handbook and Dr. Pieter Admiraal's Guide to a Humane Self-Chosen Death. [57] [58] "With the withdrawal of the barbiturate sleeping tablets from the medical prescribing list, propoxyphene has become the most common doctor-prescribed medication used by seriously ill people to end their lives." [57]

See also

Related Research Articles

<span class="mw-page-title-main">Analgesic</span> Any member of the group of drugs used to achieve analgesia, relief from pain

An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

<span class="mw-page-title-main">Hydrocodone</span> Opioid drug used in pain relief

Hydrocodone, also known as dihydrocodeinone, is a semisynthetic opioid used to treat pain and as a cough suppressant. 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 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.

<span class="mw-page-title-main">Oxycodone</span> Opioid medication

Oxycodone, sold under various brand names such as Roxicodone and OxyContin, is a semi-synthetic opioid used medically for treatment of moderate to severe pain. It is highly addictive and is a commonly abused drug. It is usually taken by mouth, and is available in immediate-release and controlled-release formulations. Onset of pain relief typically begins within fifteen minutes and lasts for up to six hours with the immediate-release formulation. In the United Kingdom, it is available by injection. Combination products are also available with paracetamol (acetaminophen), ibuprofen, naloxone, naltrexone, and aspirin.

<span class="mw-page-title-main">Paracetamol</span> Common medication for pain and fever

Paracetamol (acetaminophen) is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely used over the counter medication. Common brand names include Tylenol and Panadol.

<span class="mw-page-title-main">Naloxone</span> Opioid receptor antagonist

Naloxone is an opioid antagonist: a medication used to reverse or reduce the effects of opioids. For example, it is used to restore breathing after an opioid overdose. Effects begin within two minutes when given intravenously, five minutes when injected into a muscle, and ten minutes as a nasal spray. Naloxone blocks the effects of opioids for 30 to 90 minutes.

<span class="mw-page-title-main">Ibuprofen</span> Medication used for treating pain, fever, and inflammation

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used orally or intravenously. It typically begins working within an hour.

<span class="mw-page-title-main">Tramadol</span> Medication of the opioid type, patented 1972

Tramadol, sold under the brand name Ultram among others, is an opioid pain medication and a serotonin–norepinephrine reuptake inhibitor (SNRI) used to treat moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour. It is also available by injection. It is available in combination with paracetamol (acetaminophen).

<span class="mw-page-title-main">Opioid</span> Psychoactive chemical

Opioids are a class of drugs that derive from, or mimic, natural substances found in the opium poppy plant. Opioids work in the brain to produce a variety of effects, including pain relief. As a class of substances, they act on opioid receptors to produce morphine-like effects.

<span class="mw-page-title-main">Carisoprodol</span> Muscle relaxant medication

Carisoprodol, sold under the brand name Soma among others, is a medication used for musculoskeletal pain. Use is only approved for up to three weeks. Effects generally begin within half an hour and last for up to six hours. It is taken orally.

<span class="mw-page-title-main">Buprenorphine</span> Opioid used to treat pain & opioid use disorder

Buprenorphine, sold under the brand name Subutex among others, is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection, as a skin patch (transdermal), or as an implant. For opioid use disorder, the patient must have moderate opioid withdrawal symptoms before buprenorphine can be administered under direct observation of a health-care provider.

<span class="mw-page-title-main">Dihydrocodeine</span> Opioid

Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) or aspirin. It was developed in Germany in 1908 and first marketed in 1911.

<span class="mw-page-title-main">Butalbital</span> Barbiturate drug used for headaches

Butalbital is a barbiturate with an intermediate duration of action. Butalbital is often combined with other medications, such as paracetamol (acetaminophen) or aspirin, for the treatment of pain and headache. The various formulations combined with codeine are FDA-approved for the treatment of tension headaches. Butalbital has the same chemical formula as talbutal but a different structure—one that presents as 5-allyl-5-isobutylbarbituric acid.

<span class="mw-page-title-main">Hydrocodone/paracetamol</span> Combination pain relief drug

Hydrocodone/paracetamol is the combination of the pain medications hydrocodone and paracetamol (acetaminophen). It is used to treat moderate to severe pain. It is taken by mouth. Recreational use is common in the United States.

<span class="mw-page-title-main">Codeine</span> Opiate and prodrug of morphine used to treat pain

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 used to treat mild to moderate degrees of pain. Greater benefit may occur when combined with paracetamol (acetaminophen) or a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. Evidence does not support its use for acute cough suppression in children or adults. In Europe, it is not recommended as a cough medicine in those under 12 years of age. It is generally taken by mouth. It typically starts working after half an hour, with maximum effect at two hours. Its effects last for about four to six hours. Codeine exhibits abuse potential similar to other opioid medications, including a risk of habituation and overdose.

<span class="mw-page-title-main">Tapentadol</span> Opioid analgesic of benzenoid class

Tapentadol, brand names Nucynta among others, is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs within 32 minutes of oral administration, and lasts for 4–6 hours.

<span class="mw-page-title-main">Paracetamol poisoning</span> Toxicity due to paracetamol overdose

Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These symptoms include feeling tired, abdominal pain, or nausea. This is typically followed by absence of symptoms for a couple of days, after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment, death from toxicity occurs 4 to 18 days later.

An equianalgesic chart is a conversion chart that lists equivalent doses of analgesics. Equianalgesic charts are used for calculation of an equivalent dose between different analgesics. Tables of this general type are also available for NSAIDs, benzodiazepines, depressants, stimulants, anticholinergics and others.

<span class="mw-page-title-main">Norpropoxyphene</span> Chemical compound

Norpropoxyphene is a major metabolite of the opioid analgesic drug dextropropoxyphene, and is responsible for many of the side effects associated with use of this drug, especially the unusual toxicity seen during dextropropoxyphene overdose. It has weaker analgesic effects than dextropropoxyphene itself, but is a relatively potent pro-convulsant and blocker of sodium and potassium channels, particularly in heart tissue, which produces prolonged intracardiac conduction time and can lead to heart failure following even relatively minor overdoses. The toxicity of this metabolite makes dextropropoxyphene up to 10 times more likely to cause death following overdose compared to other similar mild opioid analgesics, and has led to dextropropoxyphene being withdrawn from the market in some countries.

<span class="mw-page-title-main">Hydrocodone/ibuprofen</span> Combination drug

Hydrocodone/ibuprofen (INNs), sold under the brand name Vicoprofen, is a fixed-dose combination analgesic medication used in short-term therapy to relieve severe pain. Vicoprofen combines the analgesic and antitussive properties of hydrocodone with the analgesic, anti-inflammatory, and antipyretic properties of ibuprofen. In contrast to hydrocodone/acetaminophen combination analgesics such as Vicodin, this hydrocodone/ibuprofen avoids some of the liver toxicity which may occur from acetaminophen, but still presents significant dangers in hydrocodone overdose, namely respiratory depression. Vicoprofen is supplied in a fixed dose combination tablet which contains hydrocodone bitartrate, USP 7.5 mg with ibuprofen, USP 200 mg. Additional strengths of generic Vicoprofen are now available, in combinations of 5 mg/200 mg and 10 mg/200 mg respectively.

<span class="mw-page-title-main">Benzhydrocodone</span> Chemical compound

Benzhydrocodone (INN) is an opioid prodrug of the morphinan class. Its chemical structure consists of hydrocodone coupled with benzoic acid. Benzhydrocodone itself is inactive and acts as a prodrug to hydrocodone upon cleavage of the benzoate portion of the molecule.

References

  1. ↑ "Drug Scheduling". Drug Enforcement Administration . Retrieved 2024-01-22.
  2. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-03.
  3. 1 2 3 4 5 Davis MP, Glare PA, Hardy J (2009) [2005]. Opioids in Cancer Pain (2nd ed.). Oxford, UK: Oxford University Press. ISBN   978-0-19-157532-7.
  4. ↑ "PRODUCT INFORMATION PARADEX" (PDF). TGA eBusiness Services. Aspen Pharmacare Australia Pty Ltd. 2 March 2010. Retrieved 9 April 2014.
  5. ↑ US 2728779,Pohland A,"Esters of Substituted Aminobutanes",issued 27 December 1955, assigned to Eli Lilly and Company.
  6. ↑ "Dextropropoxyphen". RÖMPP Online. Stuttgart: Georg Thieme Verlag KG. 30 April 2013.
  7. ↑ Gandey A (2 February 2011). "Physicians Say Good Riddance to 'Worst Drug in History'". Medscape.
  8. 1 2 3 "Dextropropoxyphene questions and answers". Therapeutic Goods Administration (TGA). Commonwealth of Australia. 7 January 2014.
  9. ↑ "Consumer Medicine Information: Digesic" (PDF). Aspen Pharmacare Australia Pty Ltd. Archived from the original (PDF) on 2009-09-14. Retrieved 2009-03-12.
  10. ↑ Nursing 2000 Drug Handbook. Springhouse, Pennsylvania: Springhouse Corp. 2000. p. 306. ISBN   978-0-87434-993-1.
  11. 1 2 British National Formulary (BNF) (57th ed.). London, UK: Pharmaceutical Press. 2009. ISBN   978-0-85369-845-6.
  12. 1 2 Barkin RL, Barkin SJ, Barkin DS (2006). "Propoxyphene (dextropropoxyphene): a critical review of a weak opioid analgesic that should remain in antiquity". American Journal of Therapeutics. 13 (6): 534–542. doi:10.1097/01.mjt.0000253850.86480.fb. PMID   17122535.
  13. ↑ "Restless legs syndrome: Definition from". Answers.com. Retrieved 2009-08-19.
  14. ↑ "Restless Leg Syndrome". Sleep Medicine Centers of WNY. Sleepmedicinecenters.com. Retrieved 2009-08-19.
  15. ↑ "Causes, diagnosis and treatment for the patient living with Restless Legs Syndrome (RLS)". Restless Leg Syndrome Foundation. 1 April 2006. Archived from the original on 2 September 2009. Retrieved 2009-08-19.
  16. ↑ Hayes CJ, Hudson TJ, Phillips MM, Bursac Z, Williams JS, Austin MA, et al. (November 2015). "The influence of propoxyphene withdrawal on opioid use in veterans". Pharmacoepidemiology and Drug Safety. 24 (11): 1180–1188. doi:10.1002/pds.3851. PMC   5305002 . PMID   26248742.
  17. ↑ "Propoxyphene Side Effects: Common, Severe, Long Term".
  18. ↑ Xiao Y (October 2001). "Blockade of Rat α3β4 Nicotinic Receptor Function by Methadone, Its Metabolites, and Structural Analogs — JPET". Journal of Pharmacology and Experimental Therapeutics. 299 (1): 366–371.
  19. ↑ "Dexedrine® (dextroamphetamine sulfate) Spansule® sustained release capsules [Label]" (PDF). US Food and Drug Administration. Amedra Pharmaceuticals LLC. February 2015. Retrieved November 11, 2016. In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.
  20. 1 2 3 Nickander RC, Emmerson JL, Hynes MD, Steinberg MI, Sullivan HR (August 1984). "Pharmacologic and toxic effects in animals of dextropropoxyphene and its major metabolite norpropoxyphene: a review". Human Toxicology. 3 (Suppl): 13S–36S. doi:10.1177/096032718400300103. PMID   6090306. S2CID   1333582.
  21. 1 2 3 Strøm J, Häggmark S, Madsen PS, Reiz S, Sørensen MB (1985). "Cardiac pacing and central hemodynamics in experimental propoxyphene induced shock". Journal of Toxicology. Clinical Toxicology. 23 (4–6): 353–6. doi:10.3109/15563658508990644. PMID   4057325.
  22. ↑ Holland DR, Steinberg MI (January 1979). "Electrophysiologic properties of propoxyphene and norpropoxyphene in canine cardiac conducting tissues in vitro and in vivo". Toxicology and Applied Pharmacology. 47 (1): 123–33. doi:10.1016/0041-008x(79)90079-6. PMID   425111.
  23. ↑ Bredgaard Sørensen M, Strøm J, Sloth Madsen P, Angelo HR, Reiz S (August 1984). "Haemodynamic, electrocardiographic and cardiometabolic changes after overdose of propoxyphene. An experimental study in pentobarbitone-anaesthetized pigs". Human Toxicology. 3 (Suppl): 53S–59S. doi:10.1177/096032718400300107. PMID   6480018. S2CID   2890957.
  24. ↑ Stork CM, Redd JT, Fine K, Hoffman RS (1995). "Propoxyphene-induced wide QRS complex dysrhythmia responsive to sodium bicarbonate--a case report". Journal of Toxicology. Clinical Toxicology. 33 (2): 179–83. doi:10.3109/15563659509000470. PMID   7897759.
  25. ↑ Wilson CO, Gisvold JH (2004). Wilson and Gisvold's textbook of organic medicinal and pharmaceutical chemistry. Lippincott Williams & Wilkins. ISBN   978-0-7817-3481-3.
  26. ↑ Kamal-Bahl SJ, Stuart BC, Beers MH (September 2006). "Propoxyphene use and risk for hip fractures in older adults". The American Journal of Geriatric Pharmacotherapy. 4 (3): 219–226. doi:10.1016/j.amjopharm.2006.09.005. PMID   17062322.
  27. ↑ Hayes CJ, Hudson TJ, Phillips MM, Bursac Z, Williams JS, Austin MA, et al. (November 2015). "The influence of propoxyphene withdrawal on opioid use in veterans". Pharmacoepidemiology and Drug Safety. 24 (11): 1180–1188. doi:10.1002/pds.3851. PMC   5305002 . PMID   26248742.
  28. ↑ "Memorandum for the U.S. Secretary of Defense" (PDF). 20 December 1977. Archived (PDF) from the original on 2017-09-16. Retrieved 2013-07-28.
  29. ↑ Erickson TJ (1986-03-01). "Asymmetric synthesis of Darvon alcohol". The Journal of Organic Chemistry. 51 (6): 934–935. doi:10.1021/jo00356a034. ISSN   0022-3263.
  30. ↑ Brown HC, Ramachandran PV (1996-08-13). "Sixty Years of Hydride Reductions". In Abdel-Magid AF (ed.). Reductions in Organic Synthesis: Recent Advances and Practical Applications. ACS Symposium Series. Vol. 641. Washington, DC: American Chemical Society. pp. 1–30. doi:10.1021/bk-1996-0641.ch001. ISBN   978-0-8412-3381-2.
  31. ↑ "FDA pulls common pain med off the market". CNN . 19 November 2010.
  32. ↑ "Safety Alerts for Human Medical Products - Propoxyphene: Withdrawal - Risk of Cardiac Toxicity". www.fda.gov. US Food and Drug Administration. November 19, 2010. Retrieved November 11, 2016.
  33. ↑ "TGA to cancel four prescription pain-killers from 1 March 2012". Therapeutic Goods Administration (TGA). Commwealth of Australia. Archived from the original on 4 December 2011. Retrieved 29 November 2011.
  34. ↑ "Darvon-N (dextropopoxyphene) - Recall and Withdrawal in Canada". Health Canada. 9 December 2002.
  35. ↑ "Questions and answers on the withdrawal of the marketing authorisations for medicines containing dextropropoxyphene" (PDF). European Medicines Agency. 25 June 2009. Archived from the original (PDF) on 2 September 2009. Retrieved 2009-09-08.
  36. ↑ "Paradex And Capadex To Be Withdrawn From NZ" . Retrieved 2010-02-21.
  37. ↑ "Govt. bans painkiller". The Hindu. 13 June 2013.
  38. ↑ "Fasta kombinationer av smärtstillande läkemedel innehållande dextropropoxifen försvinner från marknaden under hösten 2005" [Fixed combinations of analgesic drugs containing dextropropoxyphene disappear from the market in the autumn of 2005] (in Swedish). Läkemedelsverket. 5 May 2005. Archived from the original on 27 September 2007. Retrieved 22 April 2007.
  39. ↑ "Dextropropoxyphene". European Medicines Agency. 17 September 2018. On 25 June 2009, the European Medicines Agency ... recommended that all marketing authorisations for dextropropoxyphene-containing medicines should be withdrawn throughout the European Union (EU).
  40. ↑ "Dextropropoxyphene is removed from the market". Läkemedelsverket (in Swedish). 5 May 2005. Archived from the original on 22 July 2011. Retrieved 1 February 2011.
  41. ↑ "Painkiller Scrapped Over Suicides". BBC News. 31 January 2005.
  42. ↑ "Distalgesic (discontinued in the UK - December 2007)". netdoctor. 9 January 2008. Retrieved 8 September 2013.
  43. 1 2 Duff G (31 January 2005). Withdrawal of co-proxamol products and interim updated prescribing information (PDF). Medicines and Healthcare Products Regulatory Agency (Report).
  44. ↑ "Co-proxamol withdrawal: reminder to prescribers". Medicines and Healthcare products Regulatory Agency (MHRA). 11 December 2014.
  45. ↑ "Co-proxamol: outcome of the review of risks and benefits" [ permanent dead link ]. Questions and Answers leaflet, Retrieved August 28, 2009
  46. ↑ Hawton K, Bergen H, Simkin S, Brock A, Griffiths C, Romeri E, et al. (June 2009). "Effect of withdrawal of co-proxamol on prescribing and deaths from drug poisoning in England and Wales: time series analysis". BMJ. 338: b2270. doi:10.1136/bmj.b2270. PMC   3269903 . PMID   19541707.
  47. ↑ "Co-Proxamol". House of Commons debates (TheyWorkForYou.com). 13 July 2005.
  48. ↑ "Co-proxamol". Westminster Hall debates (TheyWorkForYou.com). 17 January 2007.
  49. ↑ McLean R (6 January 2008). "Failure Of MHRA Coproxamol Named Patient System". Visitor Opinion. Medical News Today. Archived from the original on 2008-11-21. Retrieved 2008-01-08.
  50. ↑ "News Centre : MHRA". Archived from the original on 2009-09-17. Retrieved 2009-08-28.
  51. ↑ Triggle N (2017-03-28). "NHS targets suncream prescriptions for cuts". BBC News. Retrieved 2017-03-28.
  52. ↑ "FDA Takes Actions on Darvon, Other Pain Medications Containing Propoxyphene". U.S. Food and Drug Administration (FDA). 7 July 2009.
  53. ↑ "Drug Information for Darvocet-N 100 Oral". Web MD.
  54. ↑ "NCQA's HEDIS Measure: Use of High Risk Medications in the Elderly" (PDF). National Committee for Quality Assurance (NCQA). Washington, D.C. Archived from the original (PDF) on February 1, 2010.
  55. ↑ Zajac A (November 19, 2010). "Darvon, Darvocet painkillers pulled from the U.S. market". L.A. Times. Archived from the original on November 22, 2010. Retrieved November 19, 2010.
  56. ↑ Lin FS, Lin WY, Lai CH, Chen CY, Lin CP, Lin TF, et al. (June 2012). "Analgesic efficacy of tramadol/acetaminophen and propoxyphene/acetaminophen for relief of postoperative wound pain". Acta Anaesthesiologica Taiwanica. 50 (2): 49–53. doi: 10.1016/j.aat.2012.05.009 . PMID   22769857.
  57. 1 2 Nitschke P, Stewart F (2006). The Peaceful Pill Handbook. U.S.: Exit International. ISBN   978-0-7817-3481-3.
  58. ↑ Admiraal P, Chabot B, Ogden RD, Rietveld A, Glerum J (2006). Guide to a Humane Self-Chosen Death (Second expanded ed.). Delft: WOZZ Foundation. ISBN   978-90-78581-01-7. OCLC   1100586437.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.