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Combination drug
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<h2 id="current-prescription-combination-drugs">Current prescription combination drugs</h2> <p class="note">For more common combination drugs, see <a href="/facts/WHO_Model_List_of_Essential_Medicines/6kmu81Xm">WHO Model List of Essential Medicines</a>.</p> <p>The combination drugs listed below are typically <a href="/facts/Prescription_drug/a2zNYPMq">available by prescription only</a>, but specific circumstances regarding a given combination's legal accessibility, or any specific regulation pertinent to ingredient quality, quantities, production standards, sourcing, etc. will vary by jurisdictions, and include: </p> <ul><li><a href="/facts/Amitriptyline/7YGkJGfr">amitriptyline</a> (<a href="/facts/Tricyclic_antidepressant/vpBLER2Q">tricyclic antidepressant</a>/TCA) combined with <a href="/facts/Perphenazine/rf2wAucn">perphenazine</a> (<a href="/facts/Typical_antipsychotic/TpHx2fqp">typical antipsychotic</a>), <a href="/facts/Trade_name/0tbWP1Sn">branded</a> <a href="/facts/Amitriptyline%2fperphenazine/Ne5wpz3p">Triavil</a></li> <li>amitriptyline and <a href="/facts/Chlordiazepoxide/d22CCSID">chlordiazepoxide</a> (<a href="/facts/Benzodiazepine/IgbJr4jy">benzodiazepine</a>), <a href="/facts/Amitriptyline%2fchlordiazepoxide/6ltGUXue">Limbitrol</a>, available in <a href="/facts/India/QW4TV4sy">India</a> and <a href="/facts/Bangladesh/NXk4f78Y">Bangladesh</a></li> <li><a href="/facts/Amlodipine/vTR2cPqe">amlodipine</a> (<a href="/facts/Calcium_channel_blocker/st91pD2K">calcium channel blocker</a>) and <a href="/facts/Benazepril/JmlHCIIU">benazepril</a> ([CE inhibitor), <a href="/facts/Amlodipine%2fbenazepril/bIjxF903">Lotrel</a></li> <li>amlodipine and <a href="/facts/Atorvastatin/2eJ0m0lz">atorvastatin</a> (<a href="/facts/Statin/ba4mes9W">statin</a>), <a href="/facts/Amlodipine%2fatorvastatin/14jE5YYs">Conduet</a></li> <li>amlodipine and <a href="/facts/Celecoxib/DqbVQYSs">celecoxib</a> (nonsteroidal anti-inflammory drug), <a href="/facts/Amlodipine%2fcelecoxib/PRX5c1m1">Consensai</a></li> <li>amlodipine and <a href="/facts/Lisinopril/uUz0kGp3">lisinopril</a> (ACE inhibitor), <a href="/facts/Lisinopril%2famlodipine/xae9rKcP">Lisonorm</a></li> <li>amlodipine and <a href="/facts/Olmesartan/oFFN8L9J">olmesartan</a> (ACE inhibitor), <a href="/facts/Amlodipine%2folmesartan/c9sxBfbl">Azor</a></li> <li>amlodipine and <a href="/facts/Valsartan/oFBA3SDq">valsartan</a> (ACE inhibitor), <a href="/facts/Amlodipine%2fvalsartan/PE5QadoM">Exforge</a></li> <li><a href="/facts/Amphetamine/yKIpLJ9E">amphetamine</a> (<a href="/facts/Stimulant/nmBdAXM5">stimulant</a>, mixed salts of the <a href="/facts/Racemic/STEagtrD">racemic</a> molecule) combining <a href="/facts/Dextroamphetamine/SoVP3mKN">dextroamphetamine</a> sulfate and D-amphetamine <a href="/facts/Saccharic_acid/Sr9M7cI6">saccharate</a>) with <a href="/facts/Levoamphetamine/0fhVn75c">levoamphetamine</a> sulfate and L-amphetamine <a href="/facts/Aspartic_acid/9DFSFPa1">aspartate</a> <a href="/facts/Monohydrate/dev82l69">monohydrate</a>, <a href="/facts/Adderall/87QufGGT">Adderall</a> by <a href="/facts/Shire_Pharmaceuticals/aPMjmuLE">Shire Pharmaceuticals</a>, MyDayis with slightly <a href="/facts/Evergreening/x1bEl18m">varying formulation</a>; the precursor of these drugs was called Oby-Rex ( see below), combined D-amphetamine with <a href="/facts/Methamphetamine/vS1jloMe">methamphetamine</a>, discontinued 1973</li> <li><a href="/facts/Bupropion/wjWDPxmr">bupropion</a> (<a href="/facts/Norepinephrine-dopamine_reuptake_inhibitor/Y4Bg2Bkd">norepinephrine-dopamine reuptake inhibitor</a>) and <a href="/facts/Naltrexone/SVduEm3W">naltrexone</a> (<a href="/facts/Opioid/EGnE2x99">opioid</a> receptor]] <a href="/facts/Antagonist/AssYgnt1">opioid antagonist</a>), <a href="/facts/Bupropion%2fnaltrexone/Q5tBkMg1">Contrave</a></li> <li><a href="/facts/Butalbital/taFxL43y">butalbital</a> (<a href="/facts/Barbiturate/d3PhtK8b">barbiturate</a>, CNS <a href="/facts/Depressant/T5A9pvLB">depressant</a>) and <a href="/facts/Caffeine/Hx6E2QC5">caffeine</a> (<a href="/facts/Eugeroic/nNnzmhNN">eugeroic</a>), Butapap</li> <li>butalbital, caffeine, and <a href="/facts/Aspirin/opMK4qLk">aspirin</a> (NSAID), Fiorinal</li> <li>butalbital, caffeine, and <a href="/facts/Acetaminophen/SNDfQWcf">acetaminophen</a>, <a href="/facts/Fioricet/JdSCDW3z">Fioricet</a></li> <li>butalbital, caffeine, acetaminophen, and <a href="/facts/Codeine/lr7WHXmX">codeine</a> (<a href="/facts/Opioid/EGnE2x99">opioid</a>), Fioricet with Codeine</li> <li><a href="/facts/Chlordiazepoxide/d22CCSID">chlordiazepoxide</a> (<a href="/facts/Benzodiazepine/IgbJr4jy">benzodiazepine</a>) and <a href="/facts/Clidinium_bromide/youRBH6p">clidinium bromide</a> (<a href="/facts/Anticholinergic/9mDjo23r">anticholinergic</a>), Librax<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a></li> <li><a href="/facts/Ephedrine/wxXefYXQ">ephedrine</a> (<a href="/facts/Sympathomimetic/IEYU5ERW">sympathomimetic</a>) and <a href="/facts/Ethylmorphine/dVlHEulD">ethylmorphine</a> (opioid) <a href="/facts/Ephedrine%2fethylmorphine/4naUSbTN">Lephotan</a></li> <li><a href="/facts/Flupentixol/lx3rT6tU">flupentixol</a> (<a href="/facts/Typical_antipsychotic/TpHx2fqp">typical antipsychotic</a>) and <a href="/facts/Melitracen/jPFFq7YE">melitracen</a> (<a href="/facts/Tricyclic_antidepressant/vpBLER2Q">tricyclic antidepressant</a>), available outside of the U.S. as <a href="/facts/Flupentixol%2fmelitracen/aXmXzq7d">Deanxit</a> by <a href="/facts/Lundbeck/Haqteyq1">Lundbeck</a></li> <li><a href="/facts/Hydrocodone/PjvCI4wN">hydrocodone</a> <a href="/facts/Bitartrate/y3yTRzUI">bitartrate</a> (<a href="/facts/Opioid_agonist/EGnE2x99">opioid agonist</a>, tablet) and acetaminophen, <a href="/facts/Hydrocodone%2facetaminophen/dvnKDv5S">Vicodin</a> by <a href="/facts/AbbVie/fn93NUuQ">AbbVie</a> contains 325 mg acetaminophen as a tablet, currently the only brand form in the <a href="/facts/United_States/P0sCdLe5">United States</a>. Norco is a tablet containing 300 mg acetaminophen, with limited availability in select countries.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> LorTab by <a href="/facts/UCB_(company)/wVCyjW91">UCB</a> is now an <a href="/facts/Elixir/GqbLsLJS">elixir</a> avauilable in limited ountries<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a></li> <li>hydrocodone and aspirin, <a href="/facts/Hydrocodone%2faspirin/W6e9CdJ7">Azdone</a></li> <li>hydrocodone and <a href="/facts/Guaifenesin/6M5ShWzC">guaifenesin</a> (<a href="/facts/Expectorant/rw9veqmh">expectorant</a>), <a href="/facts/Hydrocodone%2fguaifenesin/574Wo4cF">Obedron</a>, Flowtuss</li> <li>hydrocodone and <a href="/facts/Ibuprofen/vsKBTfVl">ibuprofen</a> (nonsteroidal anti-inflammatory]])NSAID), <a href="/facts/Hydrocodone%2fibuprofen/g8h9SMxJ">Ibudone</a></li> <li>ibuprofen and acetaminophen <a href="/facts/Intravenous/AwwuD3Nu">intravenous</a> <a href="/facts/Dosage_form/ahtNIMrF">solution</a>, <a href="/facts/Ibuprofen%2fparacetamol/gz2awj6N">Maxigesic IV</a><a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a></li> <li><a href="/facts/Nirmatrelvir/kPxu9XSK">nirmatrelvir</a> (<a href="/facts/Antiviral/Xgbd2eI2">antiviral</a>) and <a href="/facts/Ritonavir/ejvFjgsf">ritonavir</a> (antiviral), combination drug for <a href="/facts/Treatment_and_management_of_COVID-19/al0Ddhl2">treatment and management of COVID-19</a>), <a href="/facts/Nirmatrelvir%2fritonavir/l8wftVI5">Paxlovid</a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a></li> <li><a href="/facts/Omeprazole/rJNAvWSR">omeprazole</a> (<a href="/facts/Proton_pump_inhibitor/JIpwabbk">proton pump inhibitor</a>), <a href="/facts/Amoxicillin/ny596nAN">amoxicillin</a> (<a href="/facts/Antibiotic/sF1kIfxg">antibiotic</a>), and <a href="/facts/Rifabutin/snlV34I8">rifabutin</a> (anti-<a href="/facts/Tuberculosis/ggPyovAl">tuberculosis</a>), <a href="/facts/Omeprazole%2famoxicillin%2frifabutin/FJxN3gkP">Talicia</a></li> <li><a href="/facts/Olanzapine/8BhqJuPM">olanzapine</a> (<a href="/facts/Atypical_antipsychotic/PQYUYXMu">atypical antipsychotic</a>) and <a href="/facts/Fluoxetine/U28lM3Pm">fluoxetine</a> (<a href="/facts/Selective_serotonin_reuptake_inhibitor/L6jjcmEH">selective serotonin reuptake inhibitor</a>), <a href="/facts/Olanzapine%2ffluoxetine/4ug300tF">Symbyax</a></li> <li><a href="/facts/Oxycodone/mv95L2c7">oxycodone</a> (opioid) and acetaminophen, <a href="/facts/Oxycodone%2facetaminophen/PGm9pRK5">Percocet</a></li> <li>oxycodone and aspirin, <a href="/facts/Oxycodone%2faspirin/yDUDdXoI">Percodan</a></li> <li>oxycodone and <a href="/facts/Ibuprofen/vsKBTfVl">ibuprofen</a> (nonsteroidal anti-flammatory), <a href="/facts/Oxycodone%2fibuprofen/r5K56p16">Combunol</a></li> <li><a href="/facts/Phentermine/3MEx6MpP">phentermine</a> (<a href="/facts/Substituted_amphetamine/KlmrodPb">substituted amphetamine</a>, <a href="/facts/Amphetamine_derivative/KlmrodPb">amphetamine derivative</a>) and <a href="/facts/Topiramate/Bv5gScRt">topiramate</a> ([[antimigraine <a href="/facts/Phentermine%2ftopiramate/ej01aGdM">Qsymia</a> by <a href="/facts/Vivus/fnQMMPlc">Vivus</a></li> <li><a href="/facts/Phenylephrine/sf4DxQws">phenylephrine</a> (<a href="/facts/Sympathomimetic/IEYU5ERW">sympathomimetic</a>) and ketorolac (NSAID), <a href="/facts/Phenylephrine%2fketorolac/jKhmAzd5">Omidria</a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a></li> <li><a href="/facts/Pseudoephedrine/b2rMjnLv">pseudoephedrine</a> (sympathomimetic) and <a href="/facts/Carbinoxamine/4fmfsyxq">carbinoxamine</a> (anticholinergic), <a href="/facts/Pseudoephedrine%2fcarbinoxamine/e7pSuAQo">Rondec</a> <a href="/facts/Elixir/GqbLsLJS">elixir</a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a></li> <li><a href="/facts/Tramadol/R0tYqres">tramadol</a> and paracetamol, <a href="/facts/Tramadol%2fparacetamol/3dSTmhYA">Ultram</a></li></ul> <h2 id="combination-drugs-accessible-over-the-counter-otc">Combination drugs accessible over the counter (OTC)</h2> <p>Fixed-dose combination drugs for sale <a href="/facts/Over_the_counter/QI3FcgRf">over the counter</a> exist around the world, constituting doses that are tolerable to a mainstream consumer population. In the <a href="/facts/United_States/P0sCdLe5">United States</a>, items containing <a href="/facts/Ephedrine/wxXefYXQ">ephedrine</a>, <a href="/facts/Pseudoephedrine/b2rMjnLv">pseudoephedrine</a>, or <a href="/facts/Phenylpropanolamine/Bp2fDnBs">phenylpropanolamine</a> can be purchased without a <a href="/facts/Medical_prescription/4jt1T3mY">prescription</a>, albeit under strict oversight and from behind the pharmacy counter, per the <a href="/facts/Federal_drug_policy_of_the_United_States/NK3IpCrR">U.S. Federal drug law</a> titled the <a href="/facts/Combat_Methamphetamine_Epidemic_Act_of_2005/b4C3X3Xw">Combat Methamphetamine Epidemic Act of 2005</a>.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> </p><p>Fixed-dose combination drugs for sale <a href="/facts/Over_the_counter/QI3FcgRf">over the counter</a> internationally, including medicine indicated for various purposes: </p> <ul><li>aspirin and caffeine, <a href="/facts/Anacin/BPy5Vpr4">Anacin</a> by <a href="/facts/Bayer/fnYepBcG">Bayer</a>, <a href="/facts/Tablet_(pharmacy)/PcYmnjd0">tablet</a> widely available since 1916<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a></li> <li>chlorpheniramine (<a href="/facts/First-generation_antihistamine/L8azxq55">first-generation antihistamine</a>) and phenylpropanolamine (<a href="/facts/Sympathomimetic/IEYU5ERW">sympathomimetic</a>), marketed as Vernate Injection by Tutag Pharmaceuticals, a liquid solution for intramuscular injection;<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a><a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a><a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> available as the tablet Tri-Nefrin, and a syrup <a href="/facts/Elixir/GqbLsLJS">elixir</a> Altec Syrup, all available in Asia, all discontinued in U.S. by 2007.</li> <li>Coricidin by <a href="/facts/Bayer/fnYepBcG">Bayer</a>, a line of <a href="/facts/Cough_medicine/2Qe0AjMx">cough medicine</a> combining <a href="/facts/Chlorpheniramine/fuBFmrko">chlorpheniramine</a> and <a href="/facts/Dextromethorphan/Jq9UgD4M">dextromethorphan</a>; chlorpheniramine, dextromethorphan, guaifenesin, and acetaminophen is Coricidin Cold + Cough; chlorpheniramine, phenylephrine, guaifenesin, and acetaminophen is Coricidin HBP High Blood Pressure<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a></li> <li>aspirin, caffeine, and acetaminophen, <a href="/facts/Aspirin%2fparacetamol%2fcaffeine/cFU6dpgH">Excedrin</a> by Bayer<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a></li> <li><a href="/facts/Diphenhydramine/XbbIg1Nv">diphenhydramine</a> and <a href="/facts/8-chlorotheophylline/JF3jvefy">8-chlorotheophylline</a> as an <a href="/facts/Ionic_bond/R6nUJI5u">ionic bond</a> produce the compound <a href="/facts/Dimenhydrinate/MFzMNo3P">dimenhydrinate</a>, Dramamine by <a href="/facts/GlaxoSmithKline/NrnnxFNW">GlaxoSmithKline</a>.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a><a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a></li> <li><a href="/facts/Fenproporex/AG8JuwVv">fenproporex</a> and <a href="/facts/Diazepam/h7lIGqkM">diazepam</a>, Esbelcaps available in <a href="/facts/Central_America/CXKgTuxC">Central</a> and <a href="/facts/South_America/PhrFEMk7">South America</a><a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a></li> <li><a href="/facts/Fexofenadine/sLWI9VBq">fexofenadine</a> and <a href="/facts/Pseudoephedrine/b2rMjnLv">pseudoephedrine</a>, <a href="/facts/Fexofenadine%2fpseudoephedrine/HhrWh6U4">Allegra-D</a> by <a href="/facts/GlaxoSmithKline/NrnnxFNW">GlaxoSmithKline</a></li> <li><a href="/facts/Glucose/oUSkoLCD">glucose</a>, <a href="/facts/Fructose/pEqWJC2N">fructose</a> and <a href="/facts/Phosphoric_acid/l6NbwyCv">phosphoric acid</a>, <a href="/facts/Glucose%2ffructose%2fphosphoric_acid/KB6SWXdh">Emetrol for Nausea</a></li> <li><a href="/facts/Ibuprofen/vsKBTfVl">ibuprofen</a> and <a href="/facts/Famotidine/Qq6TRTtH">famotidine</a> (proton pump inhibitor), <a href="/facts/Ibuprofen%2ffamotidine/pxKt3yel">Duexis</a><a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a></li> <li>ibuprofen and diphenhydramine <a href="/facts/Citrate/EgKGQBdl">citrate</a>, <a href="/facts/Ibuprofen%2fdiphenhydramine/XbbIg1Nv">Advil PM</a></li> <li><a href="/facts/Loratadine/u3kQ4AFM">loratadine</a> and <a href="/facts/Pseudoephedrine/b2rMjnLv">pseudoephedrine</a>, <a href="/facts/Loratadine%2fpseudoephedrine/2TV8wPSE">Claritin-D</a> by <a href="/facts/AstraZeneca/KTPcnWfE">AstraZeneca</a></li> <li><a href="/facts/Naproxen_sodium/2oJdSCWq">naproxen sodium</a> and diphenhydramine hydrochloride, <a href="/facts/Naproxen%2fdiphenhydramine/uuX19WTJ">Aleve PM</a> by Bayer<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a></li> <li>naproxen sodium and pseudoephedrine, <a href="/facts/Naproxen%2fpseudoephedrine/chj4lUNL">Aleve-D</a></li> <li><a href="/facts/Oxomemazine%2fguaifenesin/Pz2S6wkt">Toplexil</a> by <a href="/facts/Aventis/rLQc448b">Aventis</a>, available in <a href="/facts/Dosage_form/ahtNIMrF">dosage forms</a> including tablet, <a href="/facts/Tincture/9FnzYB8U">tincture</a>, <a href="/facts/Elixir/GqbLsLJS">elixir</a> and <a href="/facts/Suppository/26njDQ8o">suppository</a>, <a href="/facts/Oxomemazine/wLd8zoel">oxomemazine</a> and guaifenesin, approved and available in <a href="/facts/France/CxIeIKM3">France</a>, <a href="/facts/Algeria/UXDF4Tj6">Algeria</a>, and <a href="/facts/Morocco/6ly8170M">Morocco</a><a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a></li> <li>Robitussin, a line of <a href="/facts/Cough_medicine/2Qe0AjMx">cough medicine</a> encompassing various combinations including <a href="/facts/Dextromethorphan/Jq9UgD4M">dextromethorphan</a>, acetaminophen, chlorpheniramine, doxylamine succinate, and/or guaifenesin.</li> <li>guaifenesin and phenylephrine, Sudafed PE by <a href="/facts/Merck_Group/5wXLtNQF">Merck</a></li></ul> <h2 id="combination-drugs-under-development">Combination drugs under development</h2> <ul><li><a href="/facts/MDMA%2fcitalopram/dGBuQz0G"><i>MDmalopram</i></a> <a href="/facts/Methylenedioxymethamphetamine/WYDACxGN">methylenedioxymethamphetamine</a> ("<i>Molly</i>" or "<i>Ecstasy</i>), an <a href="/facts/Empathogen/hxo3LqDS">empathogen</a>) and <a href="/facts/Citalopram/qepx3XJy">citalopram</a> (<a href="/facts/SSRI/L6jjcmEH">SSRI</a>), currently in FDA <a href="/facts/Phase_II_clinical_trial/o8hEodVu">Phase II clinical trials</a><a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> for treatment of <a href="/facts/Post-traumatic_stress_disorder/9etKu7bX">post-traumatic stress disorder</a>.</li></ul> <h2 id="combinations-drugs-for-veterinary-use">Combinations drugs for veterinary use</h2> <ul><li>Temaril-P combines <a href="/facts/Alimemazine/ru9zrWYr">alimemazine</a> (antitussive) and <a href="/facts/Prednisolone/aAB8cAPv">prednisolone</a> (<a href="/facts/Antipruritic/U9AAQd07">antipruritic</a>), suffix -P stands for "Pet" and is approved for use in dogs; has been a <a href="/facts/Generic_drug/IF6AXDVX">generic drug</a> since 2024, and substitutes alimemazine for <a href="/facts/Trimeprazine/ru9zrWYr">trimeprazine</a>, leaving in place prednisolone, equivalent to branded formula in efficacy</li> <li>Titzeol combines <a href="/facts/Tiletamine/n1a1YMPp">tiletamine</a> and <a href="/facts/Zolazepam/zdYkRJhF">zolazepam</a>, tranquilizers to sedate large animals including elephants, <a href="/facts/Giraffe/up0Jqouf">giraffes</a>, and <a href="/facts/Rhinoceroses/XPdqh7JF">rhinoceroses</a><a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a></li></ul> <h2 id="combination-drugs-no-longer-widely-available">Combination drugs no longer widely available</h2> <ul><li>Acutran by <a href="/facts/%25C3%2589lan/BYRNdzNQ">G.W. Carnrick Laboratories</a> is composed of <a href="/facts/Amfecloral/Jv2Np3tD">amfecloral</a>, a compound molecule pairing <a href="/facts/Dextroamphetamine/SoVP3mKN">dextroamphetamine</a> <a href="/facts/Sulfate/yuWVxsUf">sulfate</a> and <a href="/facts/Chloral_hydrate/KhDz2HhD">chloral hydrate</a>,<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> discontinued 1973<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a></li> <li>Ambar by <a href="/facts/Wyeth_Pharmaceuticals/oaUm9fwY">Wyeth Pharmaceuticals</a> combined <a href="/facts/Methamphetamine/vS1jloMe">methamphetamine</a> hydrochloride and <a href="/facts/Phenobarbital/G236GSuW">phenobarbital</a>; Ambar Extentab was the <a href="/facts/Modified-release_dosage/YpWevExQ">extended-release formulation</a></li> <li>Amphaplex 10 by Laderle Laboratories (later acquired by Wyeth) combined 2.5 mg methamphetamine <a href="/facts/Saccharic_acid/Sr9M7cI6">saccharate</a>, 2.5 mg methamphetamine <a href="/facts/Hydrochloride/7Sdqua4a">hydrochloride</a>, and 5 mg racemic amphetamine sulfate; Amphaplex 20 combined 5 mg methamphetamine saccharate, 5 mg methamphetamine hydrochloride, and 10 mg racemic amphetamine sulfate.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a></li> <li>Amplus Now by <a href="/facts/Pfizer/1ADDanWs">Roehrig Laboratories</a> combined 5 mg dextroamphetamine sulfate with 5 mg <a href="/facts/Hydroxyzine/tgeo6R7X">hydroxyzine</a> (first-generation antihistamine)<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a><a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a></li> <li>Amvicel by Roehrig Laboratories combined 10 mg dextroamphetamine, 40 mg <a href="/facts/Amobarbital/4SPH2Hp3">amobarbital</a>, 15 mg <a href="/facts/Phenobarbital/G236GSuW">phenobarbital</a>, 30 mg <a href="/facts/Nicotinamide/5GQcLC5K">nicotinamide</a>, plus <a href="/facts/Vitamins/SnW0LYBL">vitamins</a> and <a href="/facts/Essential_minerals/ACv8EG7f">essential minerals</a><a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a></li> <li>Apamead by Laderle Laboratories combined dextroamphetamine sulfate, amobarbital, aspirin, and phenacetin (racetin)</li> <li>ANOX by Winston Pharmaceuticals,<a href="/facts/Capsule_(pharmacy)/cVSWhU1m">encapsulated</a> <a href="/facts/Polypill/lUq0gCgm">polypill</a> combining a fixed dose of three barbiturate salts (20 mg each of <a href="/facts/Phenobarbital/G236GSuW">phenobarbital</a>, <a href="/facts/Butabarbital/pBSdT5bV">butabarbital</a>, and <a href="/facts/Secobarbital/5mgQfXgy">secobarbital</a>) and two amphetamine salts (7.5 mg each of methamphetamine hydrochloride and dextroamphetamine sulfate)<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a></li> <li>Anxine by Behlen Manufacturing<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a><a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> combined 120 mg <a href="/facts/Mephenesin/vqjI8sfS">mephenesin</a> (muscle relaxant), 35 mg <a href="/facts/Cyclobarbital/G7pssPnY">cyclobarbital</a>, and 2.5 mg dextroamphetamine sulfate</li> <li>Bama-Dex by Behlen Manufacturing combined 5 mg dextroamphetamine and 400 mg meprobamate<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a></li> <li>Biphetamine T-12.5 and Biphetamine T-20 by <a href="/facts/Fisons/rogr6Dtr">Fisons</a> comprised, respectively, 12.5 mg and 20 mg of <a href="/facts/Racemic/STEagtrD">racemic</a> amphetamine salts, thereby containing the two <a href="/facts/Enantiomers/wjPv5J3y">enantiomers</a> of <a href="/facts/Racemic_amphetamine/yKIpLJ9E">racemic amphetamine</a>, <a href="/facts/Dextroamphetamine/SoVP3mKN">dextroamphetamine</a> and <a href="/facts/Levoamphetamine/0fhVn75c">levoamphetamine</a>, at respective doses of 6.25 mg of each isomer for the former product, 10 mg of each for the latter.</li> <li>Bontril Timed No. 1 combined 2.5 mg dextroamphetamine and 7.5 mg butabarbital; Bontril Timed No. 2 5 mg dexamphetamine and 15 mg butabarbital; Bontril Timed No. 3 10 mg dexamphetamine and 30 mg butabarbital; Bontril Timed No. 4 15 mg dexamphetamine with 60 mg butabarbital, all manufactured and marketed by G.W. Carnrick Laboratories.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a></li> <li>Delcobese by Lemmon Drug Company was a balanced combination of racemic amphetamine sulfate and <a href="/facts/Adipate/yu5vJXX0">adipate</a>, "withdrawn voluntarily in 1984, unrelated to safety or legal concerns"<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a></li> <li><a href="/facts/Desbutal/E60bac93">Desbutal</a> by <a href="/facts/Union_Carbide/kCE5YHal">Irwin, Neisler & Co. (Neisler Labs)</a>, 5 mg methamphetamine and 30 mg <a href="/facts/Pentobarbital/DQgBJ2jC">pentobarbital</a>, discontinued 1973<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a></li> <li>Dexytal by <a href="/facts/Eli_Lilly/fkGYY268">Eli Lilly</a>, combination dextroamphetamine and amobarbital <a href="/facts/Elixir/GqbLsLJS">elixir</a>; <a href="/facts/Dexamyl/olCJBovc">Dexamyl</a> by Smith, French & Kline (now <a href="/facts/GlaxoSmith_Kline/NrnnxFNW">GlaxoSmith Kline</a>/GSK), dextroamphetamine and amobarbital as a tablet, discontinued 1982; Daprisal by GSK, dextroamphetamine, amobarbital, and aspirin as a tablet</li> <li>Durophet-M and Durabond, both by Neisler Labs: the former combined 12.5 mg amphetamine and 400 mg <a href="/facts/Methaqualone/B1n4znnm">methaqualone</a> (<a href="/facts/Sedative-hypnotic/JWzvq66P">sedative-hypnotic</a>), discontinued 1984 due to global convention banning methaqualone; Durabond, tablet combining 8 mg chlorpheniramine <a href="/facts/Tannate/sop1UP0T">tannate</a> (first-generation antihistamine/FGA), 25 mg <a href="/facts/Pyrilamine/XXqnuPQa">pyrilamine</a> tannate (first-generation antihistamine), and "10 mg <i>Tanphetamin</i> (racemic amphetamine tannate) [also by Neisler]"<a href="https://archive.org/stream/in.ernet.dli.2015.116604/2015.116604.General-Practice-American-Academy20_djvu.txt">"General Practice American Academy(20)"</a>. 1959.</ref></li> <li>Direcel combined dextroamphetamine, butabarbital, <a href="/facts/Carboxymethylcellulose/H9FqsRDv">carboxymethylcellulose</a>; Direcel-T included additional <a href="/facts/Thyroid_hormone/9k4xJtCq">thyroid hormone</a></li> <li>DuoDex combined <a href="/facts/Aloin/vgHP2GEm">aloin</a> (laxative), dextroamphetamine, <a href="/facts/Pentobarbital/DQgBJ2jC">pentobarbital</a>, and thyroid hormone</li> <li>Dysonil combined methamphetamine, pentobarbital, and <a href="/facts/Salicylamide/yJpTo4pf">salicylamide</a> (analgesic)</li> <li>Edrisal combined 160 mg aspirin, 160 mg <a href="/facts/Phenacetin/Ij00CRxt">phenacetin</a>, 2.5 mg amphetamine sulfate; Edrisal with Codeine included an additional 16 mg <a href="/facts/Codeine/lr7WHXmX">codeine</a></li> <li>Ethobral by Wyeth, <i>Triple-Barbiturate Tablets</i> <a href="/facts/Quinalbarbitone/5mgQfXgy">quinalbarbitone</a> sodium (rapid-acting barbiturate), <a href="/facts/Butobarbitone/ISmhd2Yt">butobarbitone</a> (intermediate-acting barbiturate), and <a href="/facts/Phenobarbital/G236GSuW">phenobarbital</a> (long-acting)<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a><a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a></li> <li><a href="/facts/Eskatrol/jRL7zonj">Eskatrol</a> by Smith, French & Kline combined dextroamphetamine and <a href="/facts/Prochlorperazine/rXCQCtU8">prochlorperazine</a> (<a href="/facts/Typical_antipsychotic/TpHx2fqp">first-generation antipsychotic</a>, discontinued 1981</li> <li>Euphoramin, 5 mg methamphetamine and 300 mg <a href="/facts/Meprobamate/6t5tc1sA">meprobamate</a>, Euphoramin</li> <li>Lamital by <a href="/facts/Teva_Pharmaceuticals/usfDATJp">Teva Pharmaceuticals</a> combines acetaminophen, amobarbital, and methamphetamine</li> <li>Mandrax by Lemmon Drug Company, tablet comprising <a href="/facts/Methaqualone/B1n4znnm">methaqualone</a> and <a href="/facts/Diphenhydramine/XbbIg1Nv">diphenhydramine</a> (<a href="/facts/First-generation_antihistamine/L8azxq55">first-generation antihistamine</a>), available in <a href="/facts/South_Africa/vvXQpLgq">South Africa</a> until 1993</li> <li>Mediatric by <a href="/facts/Janssen_Pharmaceuticals/LLI9aNQL">Janssen Pharmaceuticals</a> combined two <a href="/facts/Hormones/WFnBnINJ">hormones</a> (0.25 mg <a href="/facts/Premarin/Ss9d1kUr">Premarin</a> and 2.5 mg <a href="/facts/Methyltestosterone/2nj6vCGe">methyltestosterone</a>) with 100 mg <a href="/facts/Vitamin_c/IA2f1fTm">vitamin c</a>, <a href="/facts/B_vitamins/m6ekXy6A">b vitamins</a>, and 1 mg methamphetamine</li> <li>NalerTan by Neisler combined 12.5 mg dextroamphetamine <a href="/facts/Tannate/sop1UP0T">tannate</a>, 8 mg chlorpheniramine tannate, and 25 mg <a href="/facts/Pyrilamine/XXqnuPQa">pyrilamine</a> tannate (first-generation antihistamine) <a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a><a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a></li> <li>dextroamphetamine, amobarbital, <a href="/facts/Methylcellulose/CFP7t9MP">methylcellulose</a>, and <a href="/facts/Nutritional_supplements/SHXNNxaS">nutritional supplements</a>, brandedNexorin</li> <li><a href="/facts/Obocell/NuxAeBre">Obocell</a> by Neisler combined 5 mg dextroamphetamine <a href="/facts/Phosphate/FDGVCxUG">phosphate</a> and 25 mg <a href="/facts/Methapyrilene/1fArfJNa">methapyrilene</a> phosphate (antihistamine); Obocell-TF was identical in composition with the addition of a high-viscosity methylcellulose supplement, also by Neisler and listed as "160 mg Nitrin on the label)<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a></li> <li><a href="/facts/Obetrol/HHt2VwsD">Obetrol</a> by <a href="/facts/Abbott_Laboratories/G0uWjHK9">Abbott Laboratories</a> was a mixture of methamphetamine and dextroamphetamine salts, discontinued 1973,<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> later re-branded Oby-Rex, swapping methamphetamine for <a href="/facts/Levoamphetamine/0fhVn75c">levoamphetamine</a>, the <a href="/facts/Stereoisomer/I3kzlDE8">(s) isomer</a> of racemic amphetamine.</li> <li>Obolip combined dextroamphetamine, phenobarbital, <a href="/facts/Choline/wf9EVzfx">choline</a>, dimethionine, and methylcellulose</li> <li>Phelantin by <a href="/facts/Parke-Davis/HhJ7hzUW">Parke-Davis</a> combined 100 mg <a href="/facts/Phenytoin/uFvxbwf2">phenytoin</a> (anticonvulsant), 32 mg pentobarbital, and 2.5 mg methamphetamine<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a></li> <li>Phenephen by <a href="/facts/A.H._Robins/oaUm9fwY">A.H. Robins</a> combined <a href="/facts/Hyoscyamine/g3LEmA86">hyoscyamine</a> sulfate, phenacetin, and aspirin; Phenephen with Codeine was the aforementioned formula with codeine as a fourth <a href="/facts/Active_ingredient/oeDx5S19">active ingredient</a></li> <li>Pondimin, better known as "<a href="/facts/Fenfluramine%2fphentermine/8UBADHNB">fen-phen</a>," a <a href="/facts/Colloquialism/HvEweYjS">colloquialism</a> for combination <a href="/facts/Fenfluramine/egSpgNxd">fenfluramine</a> and <a href="/facts/Phentermine/3MEx6MpP">phentermine</a>, discontinued 1997<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a></li> <li>SynaTan-S by Neisler (later acquired by <a href="/facts/Mallinckrodt/5FJrgoMX">Mallinckrodt</a> and re-branded OboTan-S)<a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a><a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a><a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a>) combined 10 mg dextroamphetamine <a href="/facts/Tannate/sop1UP0T">tannate</a> with 35 mg secobarbital<a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a></li> <li>Pre M.T. by Behlen combined <a href="/facts/Racemic/STEagtrD">racemic</a> amphetamine sulfate, <a href="/facts/Pentobarbital/DQgBJ2jC">pentobarbital</a>, and <a href="/facts/Pyrilamine_maleate/XXqnuPQa">pyrilamine maleate</a> with a microdose of <a href="/facts/Theobromine/1L7mWzQ4">theobromine</a></li> <li>Reladorm combined 100 mg <a href="/facts/Cyclobarbitol/G7pssPnY">cyclobarbitol</a> and 10 mg <a href="/facts/Diazepam/h7lIGqkM">diazepam</a>, last available in <a href="/facts/Russia/jfkCwyxn">Russia</a> until it was discontinued in 2019<a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a></li> <li><a href="/facts/Tuinal/XwxHLHkC">Tuinal</a> by <a href="/facts/AbbVie/fn93NUuQ">AbbVie</a> was a capsule containing amobarbital and secobarbital (double barbiturate); voluntarily discontinued by AbbVie in 2008, citing widespread <a href="/facts/Substance_abuse/e3jLXFsF">substance abuse</a> as well as declining sales due to a decrease in prescriptions, and thus, demand.<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a></li></ul> <h2 id="medical-use-and-justification-of-discontinued-combination-drugs">Medical use and justification of discontinued combination drugs</h2> <p>Most of the combination drugs which have been discontinued since the twentieth century were simultaneously indicated and utilized for treatment of various conditions, with medical use justified as part of a multifaceted, comprehensive approach to patient health care and medical treatment. <a href="/facts/Central_nervous_system/k8I6To97">Central nervous system</a> <a href="/facts/Stimulant/nmBdAXM5">stimulants</a> were versatile as <a href="/facts/Anorectic/MuLF8GNo">anorectic</a>, <a href="/facts/Antidepressant/N62ND3Fa">antidepressant</a>, and <a href="/facts/Eugeroic/nNnzmhNN">eugeroic</a> (wakefulness-promoting) agents, boosting mental alertness and physical stamina, as well as the ability to maintain focus and motivation. Theoretically, when combined with a CNS <a href="/facts/Depressant/T5A9pvLB">depressant</a>, a stimulant's adverse effects (primarily overstimulation , paranoia, and/or anxiety) could be mitigated or reduced/balanced without eliminating the stimulant's therapeutic benefits. The stimulating component was almost always of the <a href="/facts/Substituted_amphetamine/KlmrodPb">substituted amphetamine</a> <a href="/facts/Chemical_class/ePAxWT8S">chemical class</a> or an <a href="/facts/Amphetamine_derivative/KlmrodPb">amphetamine derivative</a> or analog; the tranquilizing component was either one or more barbiturate salts, or non-barbiturate <a href="/facts/GABAergic/vRTeQQUG">GABAergic</a> drugs (e.g. <a href="/facts/Meprobamate/6t5tc1sA">meprobamate</a>, <a href="/facts/Methaqualone/B1n4znnm">methaqualone</a>) with a similar mechanism of action, with <a href="/facts/Anxiolytic/uEWpGca9">tranquilizing</a>, <a href="/facts/Muscle_relaxant/9jtlSa90">muscle relaxant</a>, and <a href="/facts/Sedative/JWzvq66P">sedating</a> effects. </p><p>Patients are empowered with the capability of alleviating symptoms of multiple medical conditions with the ingestion of a single dosage form, reducing the patient's <a href="/facts/Pill_burden/sE5ke3BV">pill burden</a> and consistently showing improved <a href="/facts/Compliance_(medicine)/cC0Wfj3H">medication compliance</a> scores. The <a href="/facts/American_Association_of_Orthodontists/qpgYwR7m">American Association of Orthodontists</a> asserts that fixed-dose combinations "limit clinicians' ability to customize dosing regimens,"<a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a> despite conceding that these combinations were often capable of replacing <a href="/facts/Monoamine_Oxidase_Inhibitors/obewT56a">Monoamine Oxidase Inhibitors</a> (MAOIs) in patients with <a href="/facts/Treatment-resistant_depression/0JM2IcFa">treatment-resistant depression</a> where MAOI treatment is appropriate, but where the MAOI-related dietary restrictions would otherwise hinder patient compliance. </p><p>Scientists formulating combination drugs face challenges in the development stages of multi-drug formulations such as compatibility issues among active ingredients and excipients affecting solubility and dissolution<a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a> For prescribers, if one constituent of the combination is contraindicated for a patient, the product cannot be prescribed.<a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a><a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a> </p> <h3>Limitations of currently-available combinations</h3> <p>The limitations of combination formulations currently available for treating a widely-inclusive collection of symptoms such as Tourette's is highlighted by there not being a <a href="/facts/Polypill/lUq0gCgm">polypill</a> or any combination formula period approved for treating the condition. Medication available, and sometimes used in the context of <a href="/facts/Polypharmacy/sE5ke3BV">polypharmacy</a> involves various individual medicines for treating tics and/or <a href="/facts/Generalized_anxiety_disorder/FJRBB4fM">generalized anxiety</a> or <a href="/facts/Social_anxiety_disorder/25XIzJ0o">social anxiety disorder</a> and/or <a href="/facts/Obsessive-compulsive/bIhDh4dz">obsessive-compulsive</a> anxieties with use of individual <a href="/facts/Benzodiazepines/IgbJr4jy">benzodiazepines</a> or <a href="/facts/SSRI/L6jjcmEH">SSRIs</a> for the former two conditions, and <a href="/facts/Fluvoxamine/1wmv6FLh">fluvoxamine</a> or <a href="/facts/Clomipramine/wnhL4NfS">clomipramine</a> first-line treatments for OCD and related disorders, such as <a href="/facts/Hoarding/6d2Fk059">hoarding</a> or <a href="/facts/Compulsive_decluttering/F3PwWI8F">compulsive decluttering</a>. But, where <a href="/facts/Attention-Deficit_Hyperactivity_Disorder/uSqjIyhd">Attention-Deficit Hyperactivity Disorder</a>, depression, or insomnia become a primary concern to the patient, it is only through polypharmacy (in this case, adding another antidepressant or a "booster, alongside a <a href="/facts/Hypnotic/0SBVYkMe">hypnotic</a> soporific agent, and/or <a href="/facts/Psychostimulant/nmBdAXM5">psychostimulants</a> to both treat ADHD and counteract the <a href="/facts/Sleep_inertia/YHHQhDpH">sleep inertia</a>, grogginess or hangover caused by the other evening medications). </p><p><a href="/facts/Tourette_syndrome/YRRX4Aw4">Tourette syndrome</a> is a <a href="/facts/Neurological_disorder/eQKKs7jX">neurological</a> <a href="/facts/Tic_disorder/3sFeE8vr">tic disorder</a> for which treatment options are currently limited; only the <a href="/facts/Typical_antipsychotic/TpHx2fqp">typical antipsychotics</a>, <a href="/facts/Pimozide/FmQ8Jy4y">pimozide</a> and <a href="/facts/Haloperidol/ue4TJKmu">haloperidol</a> are specifically approved for treating the <a href="/facts/Tic/K2LnV0ll">tic</a> component of Tourette's;<a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> <a href="/facts/Clonidine/xPebaeST">clonidine</a> and <a href="/facts/Guanfacine/kXNP14wn">guanfacine</a> are approved for ADHD, which often comorbid to Tourette's, but not necessarily guaranteed to reduce tics. Typically identified by chronic motor and vocal tics (described by <a href="/facts/NIH/G3Eytfcc">NIH</a> as "semi-voluntary" actions performed in response to a <a href="/facts/Premonitory_urge/5cBoT6zz">premonitory urge</a>, an internal sensory phenomenon akin to a buildup of tension, only able to be alleviated upon releasing a tic.<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a> Tourette's, however, is an all-encompassing <a href="/facts/Blanket_terminology/bjxUuoRb">umbrella term</a> that presents not just as chronic motor/physical and vocal/phonic tics; tics are nearly always <a href="/facts/Comorbid/tX5TvuKJ">comorbid</a> to symptoms of <a href="/facts/Obsessive-compulsive/bIhDh4dz">obsessive-compulsive</a> anxiety and/or <a href="/facts/Social_anxiety/lQ2FBqUf">social anxiety</a>, <a href="/facts/Avoidant_personality_disorder/0oYpmo4J">avoidant personality</a> or <a href="/facts/Schizoid_personality/A9QXVE1s">schizoid personality</a>, <a href="/facts/ADHD/uSqjIyhd">ADHD</a>, as well as insomnia, depression, and traits of high-functioning autism (formerly "<a href="/facts/Asperger_syndrome/TUpuw6Nn">Asperger syndrome</a>"). </p> <h2 id="illicit-street-drug-combinations">Illicit "street" drug combinations</h2> <p>So-called "powder cocaine" often contains <a href="/facts/Stimulant/nmBdAXM5">stimulants</a> meant to mimic cocaine's effects; many batches analyzed did not contain any cocaine or <a href="/facts/Coca/oXhbteWq">coca</a> alkaloids at all; most frequently, "powder cocaine" is found to contain <a href="/facts/Designer_drugs/QWFd3KV4">designer drugs</a> and/or <a href="/facts/Research_chemicals/NLezxugr">research chemicals</a> including <a href="/facts/Synthetic_cathinones/6p5r2YLm">synthetic cathinones</a>, <a href="/facts/MDMA/WYDACxGN">MDMA</a>, <a href="/facts/Methamphetamine/vS1jloMe">methamphetamine</a>, <a href="/facts/Caffeine/Hx6E2QC5">caffeine</a>, and increasingly the flesh-eating veterinary antibiotic <a href="/facts/Levamisole/1XGQzV6c">levamisole</a> have been found in "powder cocaine."<a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a> </p><p>Since the forced closure of so many <a href="/facts/Pill_mill/JnED7wWt">pill mills</a> in the U.S. beginning in 2007, a <a href="/facts/Black_market/HDL3tQDz">black market</a> for opioids has flourished and continuously expanded.<a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a> As demand increases for relatively mild opioid "pain pills" ranging from codeine, hydrocodone, oxycodone, morphine, <a href="/facts/Diacetylmorphine/rYwrKHPk">diacetylmorphine</a> (Heroin) items being deceptively sold as such are <a href="/facts/Adulterant/fM78Wcvc">adulterated</a> by undeclared amounts of highly potent <a href="/facts/Synthetic_opioid/EGnE2x99">synthetic opioids</a> of questionable purity. <a href="/facts/Prince/g6CDfwEJ">Prince</a> <a href="/facts/Death_of_Prince/cSkbYHIA">died in April 2016</a> from taking pills he thought were "<a href="/facts/Percocet/PGm9pRK5">Percocet</a>;" in actuality, the "Percocet" was not relatively mild oxycodone, but <a href="/facts/Counterfeit_medication/a1bqeWde">counterfeit "presses" or "pressed pills"</a> that resulted in Prince's gradual ingestion of unknown, but lethal, quantities of <a href="/facts/Fentanyl/MMD9GdD3">fentanyl</a>. "Presses" are synthesized via <a href="/facts/Clandestine_chemistry/7h0ljKSs">clandestine chemistry</a> by untrained chemists and often <a href="/facts/Cutting_agent/PJ5WLbDp">cut with agents</a> including fentanyl, <a href="/facts/Carfentanil/bCnYQJhh">carfentanil</a>, and as of September 2024, <a href="/facts/Nitazene/LNLzIfQy">nitazenes</a>.<a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a><a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a> </p><p>Other <a href="/facts/Cutting_agent/PJ5WLbDp">cutting agents</a> increasingly found in illicit supplies include the veterinary drug <a href="/facts/Xylazine/3fkrmSN6">xylazine</a> and the <a href="/facts/Designer_drug/QWFd3KV4">designer drugs</a> (synthetic <a href="/facts/Triazolobenzodiazepine/6TorVdwk">triazolobenzodiazepines</a>) <a href="/facts/Bromazolam/qGtgUabq">bromazolam</a>, <a href="/facts/Clobromazolam/CWKwEN7W">clobromazolam</a>, <a href="/facts/Phenazolam/CWKwEN7W">phenazolam</a>, and <a href="/facts/Flualprazolam/BVN0GcXS">flualprazolam</a>.<a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a> In April 2025, <a href="/facts/U.S._Attorney_General/8VaY1rlI">U.S. Attorney General</a> <a href="/facts/Pam_Bondi/Sq54dIk0">Pam Bondi</a> stated a desire to regulate xylazine under <a href="/facts/Controlled_Substances_Act/8laeNsgD">U.S. federal drug law</a>) as a <a href="/facts/Controlled_substance/Hx9cKG4f">Schedule III controlled substance</a>.<a class="footnote-ref" id="fnref:65" href="#fn:65"><sup>65</sup></a> Xylazine is currently a controlled substance under state statutes in <a href="/facts/Michigan/bCurmfT2">Michigan</a> and <a href="/facts/New_York_(state)/mnl67G1G">New York</a>.<a class="footnote-ref" id="fnref:66" href="#fn:66"><sup>66</sup></a> </p><p>Mandrax is the trade name of a pharmaceutical combination drug consisting of <a href="/facts/Methaqualone/B1n4znnm">methaqualone</a> and <a href="/facts/Diphenhydramine/XbbIg1Nv">diphenhydramine</a>.,<a class="footnote-ref" id="fnref:67" href="#fn:67"><sup>67</sup></a> once prescribed in <a href="/facts/South_Africa/vvXQpLgq">South Africa</a>, but banned in 1993. "Mandrax" is now synthesized via <a href="/facts/Clandestine_chemistry/7h0ljKSs">clandestine chemistry</a> as a <a href="/facts/Free_base/bLMkVbTk">free base</a> preparation, which is smoked for an intense, short-lived <a href="/facts/Substance_intoxication/LRnMxrKd">"high"</a>.<a class="footnote-ref" id="fnref:68" href="#fn:68"><sup>68</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Codrug/DTrSpkbA">Codrugs</a></li> <li><a href="/facts/Synergy/lfcwWuAc">Synergy#Drug synergy</a></li></ul> <h2 id="external-links">External links</h2> <ul><li> Media related to Combination drugs at Wikimedia Commons</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Martin, Mike (2009-04-01). "5-in-1 PolyPill Treatment May Prevent Heart Disease". www.bayviewrx.com. Archived from the original on 2014-02-27. <a href="https://web.archive.org/web/20140227164714/http://www.bayviewrx.com/bayview-blog/bid/18766/5-in-1-PolyPill-Treatment-May-Prevent-Heart-Disease" target="_blank">https://web.archive.org/web/20140227164714/http://www.bayviewrx.com/bayview-blog/bid/18766/5-in-1-PolyPill-Treatment-May-Prevent-Heart-Disease</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Grobbee'], ['Diederick E. "Cardioprotective Drugs: Polypills".{{cite web}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link) <a href="https://www.escardio.org/Education/ESC-Prevention-of-CVD-Programme/Treatment-goals/Cardio-Protective-drugs/polypills" target="_blank">https://www.escardio.org/Education/ESC-Prevention-of-CVD-Programme/Treatment-goals/Cardio-Protective-drugs/polypills</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"The Compounder - Amino Acids, Minerals, Nutrients & Vitamins". <a href="https://thecompounder.com/amino-acids-minerals-nutrients-vitamins/" target="_blank">https://thecompounder.com/amino-acids-minerals-nutrients-vitamins/</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Antiretroviral Drug Discovery and Development". National Institutes of Health. 5 February 2024. 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Retrieved April 26, 2025. <a href="https://www.heart.org/en/health-topics/heart-attack/treatment-of-a-heart-attack/aspirin-and-heart-disease" target="_blank">https://www.heart.org/en/health-topics/heart-attack/treatment-of-a-heart-attack/aspirin-and-heart-disease</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>"Dimenhydrinate". National Institute of Diabetes and Digestive and Kidney Diseases. 2012. 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