Combination drug

This article is about fixed-dose combination drugs and polypills as treatments. For two synergistic drugs chemically linked together, see codrug. For use of multiple separate and individual drugs for treatment, see polypharmacy.

A combination drug is an approved pharmaceutical formulation that has been manufactured in a single dosage form, e.g. as a pill, the colloquialism for capsule, tablet, caplet, or softgel gelcaps, all of which have been colloquially called a "pill," though flavored elixirs ("syrups") are often available as a secondary administration method for patients who are unable or unwilling to swallow a pill. Currently, the market for such medications as a tincture or suppository is low; thus, only select brands offer this option. Vitamins and minerals, nutritional supplements, and hormones may also be included for the maximum treatment potential. Either ingredient may be an over-the-counter drug or a prescription drug, and some combination drugs include additional synthetic pharmaceutical drugs or hormones, while others may balance pharmaceuticals with naturally-occurring, plant-based alkaloids or herbal extract.

Fixed-dose combination drugs were initially developed to target a single disease, as with antiretroviral FDCs indicated for treating AIDS and HIV.^[1] Combination drug treatment conceptually emphasizes simplified treatment plans, reduced pill burden and increased patient compliance by offering accessible and affordable ingredients, generally generic drugs with established therapeutic efficacy, and the ability to treat a variety of symptoms and conditions amongst a large patient population with varying treatment needs.

A polypill is a tablet or capsule containing four or more active ingredients,^[2][3] frequently requiring custom preparation at a compounding pharmacy in order to meet the personalized specifications deemed necessary by a patient's medical prescription. Such specificities may include uncommon, unconventional, or unavailable dosage, dosage form, a modified release mechanism, and necessity for a particular speed of onset and/or duration of action. Polypills can encompass four or more of any combination of approved prescription drugs and over the counter drugs, and may also include nutritional supplements, amino acids, enzymes, hormones, vitamins and/or essential minerals.^[4]

Current prescription combination drugs

For more common combination drugs, see WHO Model List of Essential Medicines.

The combination drugs listed below are universally available by prescription only, 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:^[5]

• amitriptyline (tricyclic antidepressant) and perphenazine (typical antipsychotic), brand name Triavil
• amitriptyline and chlordiazepoxide (benzodiazepine), Limbitrol-H, available in the United States, India,^[6][7][8] and Bangladesh
• amlodipine (calcium channel blocker) and benazepril (ACE inhibitor), Lotrel
• amlodipine and atorvastatin (statin), Conduet
• amlodipine and celecoxib (nonsteroidal anti-inflammatory drug), Consensai
• amlodipine and lisinopril (ACE inhibitor), Lisonorm
• amlodipine and olmesartan (ACE inhibitor), Azor
• amlodipine and valsartan (ACE inhibitor), Exforge
• amphetamine (stimulant) racemic salt mixture, combining the enantiomer dextroamphetamine (sulfate ans saccharate bonds) and the stereoisomer levoamphetamine (sulfate and aspartate monohydrate bonds), Adderall by Shire Pharmaceuticals, MyDayis with slightly varying formulation
• bupropion (norepinephrine-dopamine reuptake inhibitor) and naltrexone (opioid antagonist), Contrave
• butalbital (barbiturate, CNS depressant) and caffeine (eugeroic), Butapap
• butalbital, caffeine, and aspirin (NSAID), Fiorinal
• butalbital, caffeine, and acetaminophen, Fioricet
• butalbital, caffeine, acetaminophen, and codeine (opioid), Fioricet with Codeine
• chlordiazepoxide (benzodiazepine) and clidinium bromide (anticholinergic), Librax^[9][10]
• ephedrine (sympathomimetic) and ethylmorphine (opioid) Lephotan
• flupentixol (typical antipsychotic) and melitracen (tricyclic antidepressant), available outside of the U.S. as Deanxit by Lundbeck
• hydrocodone bitartrate (opioid agonist, tablet) and acetaminophen, Vicodin by AbbVie contains 325 mg acetaminophen as a tablet, currently the only brand form in the United States. Norco is a tablet containing 300 mg acetaminophen, with limited availability in select countries.^[11] LorTab by UCB is now solely available as a syrup in the U.S.^[12]
• hydrocodone and aspirin, Azdone
• hydrocodone and guaifenesin (expectorant), Obedron, Flowtuss
• hydrocodone and ibuprofen (nonsteroidal anti-inflammatory]])NSAID), Ibudone
• ibuprofen and acetaminophen intravenous solution, Maxigesic IV^[13]
• nirmatrelvir (antiviral) and ritonavir (antiviral), combination drug for treatment and management of COVID-19), Paxlovid^[14]
• omeprazole (proton pump inhibitor), amoxicillin (antibiotic), and rifabutin (anti-tuberculosis), Talicia
• olanzapine (atypical antipsychotic) and fluoxetine (selective serotonin reuptake inhibitor), Symbyax
• oxycodone (opioid) and acetaminophen, Percocet
• oxycodone and aspirin, Percodan
• oxycodone and ibuprofen (nonsteroidal anti-flammatory), Combunol
• phentermine (substituted amphetamine, amphetamine derivative) and topiramate (antimigraine) Qsymia by Vivus
• phenylephrine (sympathomimetic) and ketorolac (NSAID), Omidria^[15]
• pseudoephedrine (sympathomimetic) and carbinoxamine (anticholinergic), Rondec elixir^[16]
• tramadol and paracetamol, Ultram

Combination drugs accessible over the counter (OTC)

Fixed-dose combination drugs for sale over the counter exist around the world, constituting doses that are tolerable to a mainstream consumer population. In the United States, items containing ephedrine, pseudoephedrine, or phenylpropanolamine can be purchased without a prescription, albeit under strict oversight and from behind the pharmacy counter, per the U.S. Federal drug law titled the Combat Methamphetamine Epidemic Act of 2005.^[17]

Fixed-dose combination drugs for sale over the counter internationally, including medicine indicated for various purposes:

• aspirin and caffeine, Anacin by Bayer, tablet widely available since 1916^[18]
• chlorpheniramine (first-generation antihistamine) and phenylpropanolamine (sympathomimetic), marketed as Vernate Injection by Tutag Pharmaceuticals, a liquid solution for intramuscular injection;^[19][20][21] available as the tablet Tri-Nefrin, and a syrup elixir Altec Syrup, all available in Asia, all discontinued in U.S. by 2007.
• Coricidin by Bayer, a line of cough medicine combining chlorpheniramine and dextromethorphan; chlorpheniramine, dextromethorphan, guaifenesin, and acetaminophen is Coricidin Cold + Cough; chlorpheniramine, phenylephrine, guaifenesin, and acetaminophen is Coricidin HBP High Blood Pressure^[22]
• aspirin, caffeine, and acetaminophen, Excedrin by Bayer^[23]
• diphenhydramine and 8-chlorotheophylline as an ionic bond produce the compound dimenhydrinate, Dramamine by GlaxoSmithKline.^[24][25]
• fenproporex and diazepam, Esbelcaps available in Central and South America^[26]
• fexofenadine and pseudoephedrine, Allegra-D by GlaxoSmithKline
• glucose, fructose and phosphoric acid, Emetrol for Nausea
• ibuprofen and famotidine (proton pump inhibitor), Duexis^[27]
• ibuprofen and diphenhydramine citrate, Advil PM
• loratadine and pseudoephedrine, Claritin-D by AstraZeneca
• naproxen sodium and diphenhydramine hydrochloride, Aleve PM by Bayer^[28]
• naproxen sodium and pseudoephedrine, Aleve-D
• Toplexil by Aventis, available in dosage forms including tablet, tincture, elixir and suppository, oxomemazine and guaifenesin, approved and available in France, Algeria, and Morocco^[29]
• Robitussin, a line of cough medicine encompassing various combinations including dextromethorphan, acetaminophen, chlorpheniramine, doxylamine succinate, and/or guaifenesin.
• guaifenesin and phenylephrine, Sudafed PE by Merck

Combination drugs under development

• MDmalopram methylenedioxymethamphetamine ("Molly" or "Ecstasy), an empathogen) and citalopram (SSRI), currently in FDA Phase II clinical trials^[30] for treatment of post-traumatic stress disorder.

Combinations drugs for veterinary use

• Temaril-P combines alimemazine (antitussive) and prednisolone (antipruritic), suffix -P stands for "Pet" and is approved for use in dogs; has been a generic drug since 2024, and substitutes alimemazine for trimeprazine, leaving in place prednisolone, equivalent to branded formula in efficacy
• Titzeol combines tiletamine and zolazepam, tranquilizers to sedate large animals including elephants, giraffes, and rhinoceroses^[31]

Combination drugs no longer available

Fisons Research Laboratories

• Biphetamine T-12.5 and Biphetamine T-20 by Fisons, respectively contained one-half (6.25 and 10, reectively) of each isomer of the racemic amphetamine molecule. T-20 therefore was 1/2 d and 1/2 l contained 20 mg; thus each formulation contained a 1:1, equally-proportioned ratio (racemic) proptionate ratio of the stereoisomers dextroamphetamine and levoamphetamine.

=G.W. Carnrick Laboratories, acquired by Élan Pharmaceuticals of Ireland

• Acutran by G.W. Carnrick Laboratories is composed of amfecloral, a compound molecule pairing dextroamphetamine sulfate and chloral hydrate,^[32] discontinued 1973^[33]
• 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.^[34]

=Laderle Laboratories, Roehrig Labs, and Wyeth Pharma: all now Pfizer

• Amphaplex 10 by Laderle Laboratories (later acquired by Wyeth) combined 2.5 mg methamphetamine saccharate, 2.5 mg methamphetamine hydrochloride, and 5 mg racemic amphetamine sulfate; Amphaplex 20 combined 5 mg methamphetamine saccharate, 5 mg methamphetamine hydrochloride, and 10 mg racemic amphetamine sulfate.^[35]

Roehrig

• Amplus Now by Roehrig Laboratories combined 5 mg dextroamphetamine sulfate with 5 mg hydroxyzine (first-generation antihistamine)^[36][37]
• Amvicel by Roehrig combined 10 mg dextroamphetamine, 40 mg amobarbital, 15 mg phenobarbital, 30 mg nicotinamide, plus vitamins and essential minerals^[38]
• Apamead by Laderle combined dextroamphetamine sulfate, amobarbital, aspirin, phenacetin
• Ambar by Wyeth Pharmaceuticals combined methamphetamine hydrochloride and phenobarbital; available asAmbar Extentab in extended-release formulation

=Winston Pharmaceuticals of Winston-Salem, N.C.

• ANOX, encapsulated polypill combining a fixed dose of three barbiturate salts (20 mg each of phenobarbital, butabarbital, and secobarbital) and two amphetamine salts (7.5 mg each of methamphetamine hydrochloride and dextroamphetamine sulfate)^[39]
• ANOX D14cel5 There is a long-acting formulation discontinued around 1966

Behlen Manufacturing

• Anxine by Behlen Manufacturing^[40][41] 120 mg mephenesin (muscle relaxant), 35 mg cyclobarbital, and 2.5 mg dextroamphetamine
• Bama-Dex combined 5 mg dextroamphetamine and 400 mg meprobamate^[42]

Lemmon Drug Co.

• Delcobese by Lemmon Drug Company was a balanced combination of racemic amphetamine sulfate and adipate, "withdrawn voluntarily in 1984, unrelated to safety or legal concerns"^[43]
• Mandrax by Lemmon Drug Company, tablet comprising methaqualone and diphenhydramine (first-generation antihistamine), available in South Africa until 1993
• Mandrax by Lemmon Drug Company, tablet comprising methaqualone and diphenhydramine (first-generation antihistamine), available in South Africa until 1993

Union Carbide

• Desbutal by Irwin, Neisler & Co. doing business as Neisler Labs, 5 mg methamphetamine and 30 mg pentobarbital, discontinued 1973^[33]

Open market of dextroamphetamine and amylbarbitone tablets

Eli Lilly & Co. Pharmaceuticals

• Dexytal by Eli Lilly, combination dextroamphetamine and amobarbital elixir;
  • Dexamyl tablet by Smith, French & Kline, acquired in 2025 by GlaxoSmith Kline), discontinued 1982

Irwin, Neisler & Co. (D/B/A Neisler Laboratories), now a division of Union Carbide

• Durophet (racemic amphetamine salts) became generized as "biphetamine" due to the nationwide ubiquity of colloquially "viphetamine]]comparable to Biphetamine by Fisons, see above) brand the former combined 12.5 mg amphetamine and 400 mg methaqualone (sedative-hypnotic), discontinued 1984 due to global convention banning methaqualone; Durabond, tablet combining 8 mg chlorpheniramine tannate (first-generation antihistamine/FGA), 25 mg pyrilamine tannate (first-generation antihistamine), and "10 mg Tanphetamin (racemic amphetamine tannate) [also by Neisler]""General Practice American Academy(20)". 1959.
• Edrisal by Wyeth, combined 160 mg aspirin, 160 mg phenacetin, 2.5 mg amphetamine /sulfate; Edrisal with Codeine included an additional 16 mg codeine^{[citation needed]}
• Ethobral by Wyeth, Triple-Barbiturate Tablets quinalbarbitone sodium (rapid-acting barbiturate), butobarbitone (intermediate-acting barbiturate), and phenobarbital (long-acting)^[44][45]

• Direcel combination dextroamphetamine, butabarbital, carboxymethylcellulose
• DuoDex, combination barbaloin (stimulant-laxative),^[46] dextroamphetamine (stimulant), pentobarbital (barbiturate), thyroid (hormone); The U.S. FDA declared in May 2002 that "aloin-containing laxatives are no longer GRAS [nor] effective for OTC use" upon the IARC classifying whole-leaf herbal extracts of aloe vera as "possibly carcinogenic to humans" due to presence of latex.
• Dysonil combined methamphetamine, pentobarbital, and salicylamide (analgesic)

Jannsen Pharmaceuticals

• Mediatric by Janssen Pharmaceuticals combined two hormones (0.25 mg Premarin and 2.5 mg methyltestosterone) with 100 mg vitamin c, b vitamins, and 1 mg methamphetamine** Daprisal by GSK, dextroamphetamine, amobarbital, and aspirin as a tablet

Smith, Kline & French, later acquired by GlaxoSmith Kline

• Eskatrol by Smith, French & Kline combined dextroamphetamine and prochlorperazine (first-generation antipsychotic, discontinued 1981
• Daprisal by GSK, dextroamphetamine, amobarbital, and aspirin as a tablet

• Euphoramin, 5 mg methamphetamine and 300 mg meprobamate (non-barbiturate, barbiturate-adjacent GABergic minor tranquilizer, sedative

Teva Pharmaceuticals

• Lamital by Teva Pharmaceuticals combines acetaminophen, sodium amylbarbitone, methamphetamine

• NalerTan by Neisler combined 12.5 mg dextroamphetamine tannate, 8 mg chlorpheniramine tannate, and 25 mg pyrilamine tannate (first-generation antihistamine) ^[47][48]
• dextroamphetamine, amobarbital, methylcellulose, and nutritional supplements, brandedNexorin
• Obocell by Neisler combined 5 mg dextroamphetamine phosphate and 25 mg methapyrilene 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)^[49]
• Obetrol by Abbott Laboratories was a mixture of methamphetamine and dextroamphetamine salts, discontinued 1973,^[33] later re-branded Oby-Rex, swapping methamphetamine for levoamphetamine, the (s) isomer of racemic amphetamine.
• Obolip combined dextroamphetamine, phenobarbital, choline, di-methionine, and methylcellulose
• Phelantin by Parke-Davis combined 100 mg phenytoin (anticonvulsant), 32 mg pentobarbital, and 2.5 mg methamphetamine^[50]
• Phenephen by A.H. Robins combined hyoscyamine sulfate, phenacetin, and aspirin; Phenephen with Codeine was the aforementioned formula with codeine as a fourth active ingredient
• Pondimin, better known as "fen-phen," a colloquialism for combination fenfluramine and phentermine, discontinued 1997^[51]
• SynaTan-S by Neisler (later acquired by Mallinckrodt and re-branded OboTan-S)^[52][53][54]) combined 10 mg dextroamphetamine tannate with 35 mg secobarbital^[55]

Polish swlzki Farmc

• Reladorm combined 100 mg cyclobarbitol and 10 mg diazepam, last available in Russia until it was discontinued in 2019^[56]

===Abbott, now a division of AbbVie

• Tuinal by AbbVie was a capsule containing amobarbital and secobarbital (double barbiturate); voluntarily discontinued by AbbVie in 2008, citing widespread substance abuse as well as declining sales due to a decrease in prescriptions, and thus, demand.^[57]

Medical use and justification of discontinued combination drugs

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. Central nervous system stimulants were versatile as anorectic, antidepressant, and eugeroic (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 depressant, 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 substituted amphetamine chemical class or an amphetamine derivative or analog; the tranquilizing component was either one or more barbiturate salts, or non-barbiturate GABAergic drugs (e.g. meprobamate, methaqualone) with a similar mechanism of action, with tranquilizing, muscle relaxant, and sedating effects.

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 pill burden and consistently showing improved medication compliance scores. The American Association of Orthodontists asserts that fixed-dose combinations "limit clinicians' ability to customize dosing regimens,"^[58] despite conceding that these combinations were often capable of replacing Monoamine Oxidase Inhibitors (MAOIs) in patients with treatment-resistant depression where MAOI treatment is appropriate, but where the MAOI-related dietary restrictions would otherwise hinder patient compliance.

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.^[59] For prescribers, if one constituent of the combination is contraindicated for a patient, the product cannot be prescribed.^[60][61]

Limitations of polypharmacy for multi-faceted disorders

Examples including neurological disorders, excessive motor activity

The limitations of combination formulations currently available for treating the large number of overlapping neurological symptoms inherent to most neurological conditions is a hindrance to properly treating disruptive, concurrent symptoms. Tourette's is a stellar example of this dilemma, because the minimum diagnostic criteria is habitual, repeated physical movements, muscle spasms, the compulsive need to repeat motions and succumb to the premonitory urge to release perform needless, disruptive central nervous system] motor activity (physical "motor tics"). Pimozide and off-label medications canhelp reduce those symptoms.

obsessive-compulsive anxiety, social anxiety, generalized anxiety, are very likely to concur with with tics; as such, polypharmacy necessitates secondary or even tertiary solutions to treat these aspects of the broader condition: OCD alone is often resolved clomipramine (a tricyclic antideresant) anxietys with use of individual benzodiazepines or SSRIs for the former two conditions, and fluvoxamine or clomipramine first-line treatments for OCD and related disorders, such as hoarding or compulsive decluttering. But, where Attention-Deficit Hyperactivity Disorder, 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 hypnotic soporific agent, and/or psychostimulants to both treat ADHD and counteract the sleep inertia, grogginess or hangover caused by the other evening medications). Tourette's Syndrome is a neurological disorder, idand is ideallt diagnosed and, to the extent possible and treated by a medical specialis trained in the field of neurologyin with neurologt tresatmentand by a neurologistideally treated by a neurologists. Tourette's is almost universally viewed as a tic disorder]], while neurotypicasl observers are unlikely to conjure the word "Tourette," or consider other forms of presentation, much less to anakyze and compare existenceunlikely to even consider the condition, but to the general public there is a conviction that use is routinely and uncontrollably engaging in disruptive, unmistakable, physical movements ("motor tics") and/or spending nearly every waking hour producing loud, disruotive, unmistkable, clearly uncmfortbe or ainful noises, grunts, grws or which treatment options are currently limited; only the typical antipsychotics, pimozide and haloperidol are specifically approved for treating the tic component of Tourette's;^[62] clonidine and guanfacine 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 NIH as "semi-voluntary" actions performed in response to a premonitory urge, an internal sensory phenomenon akin to a buildup of tension, only able to be alleviated upon releasing a tic.^[63] Tourette's, however, is an all-encompassing umbrella term that presents not just as chronic motor/physical and vocal/phonic tics; tics are nearly always comorbid to symptoms of obsessive-compulsive anxiety and/or social anxiety, avoidant personality or schizoid personality, ADHD, as well as insomnia, depression, and traits of high-functioning autism (formerly "Asperger syndrome").

being able to wal into a local pharmacy andfndking thr exact fixed dse thy need

Pimozide (approved); tetrabenazine, topiramate, diazepam, haloperidol (off label) specific to tics

For Tourette's, there is one approved, pharmaceutical directly responsible for blocking the D2 receptor – pimozide. C] and even more so to excessive motor activity (e.g.convulsions; tremors; muscle spasms; and the restlessness inherent to akathisia, the most severe, pervasive, unwaveing obsessive comulsion to move and flail entire portions lest the gradual feelingcompulsion to|general restless, and the and restlessness due to the compulsion to perform a physical motion/motor activity; NOTE: all of the aforementioned symptoms are due to the gradual rise in tension and discomfort until it is painful do without succumbing to the urge. cal tics, sounds grunts, etc. appsroved for medical use by the Food and Drug Administration (FDA), and neither of them are guaranteed to work the same for each individual, thus, treatment options are complex to identify, and difficult in that sense. For decades, the typical antipsychotic, pimozide was the sole treatment with the most targeted effect on symptoms of Tourette's particular motor tics. consist of two, o

Illicit "street" drug combinations

Terms for stimulants being sold as "powder cocaine" or crack cocaine have been found to contain as little 15% cocaine hydrochloride or any other form of ingredient with an acceptable amount of coca alkaloids at all. ABC News has conducted several investigative journalism analyses and metanalyses and have reported that the greatest concern for any so-called "cocaine" or amphetamine, methamphetamine powders and mostd found to contain designer drugs and/or research chemicals including synthetic cathinones, MDMA, methamphetamine, caffeine, and increasingly the flesh-eating veterinary antibiotic levamisole have been found in "powder cocaine."^[64]

Since the forced closure of so many pill mills in the U.S. beginning in 2007, a black market for opioids has flourished and continuously expanded.^[65] As demand increases for relatively mild opioid "pain pills" ranging from codeine, hydrocodone, oxycodone, morphine, diacetylmorphine (Heroin) items being deceptively sold as such are adulterated by undeclared amounts of highly potent synthetic opioids of questionable purity. Prince died in April 2016 from taking pills he thought were "Percocet;" in actuality, the "Percocet" was not relatively mild oxycodone, but counterfeit "presses" or "pressed pills" that resulted in Prince's gradual ingestion of unknown, but lethal, quantities of fentanyl. "Presses" are synthesized via clandestine chemistry by untrained chemists and often cut with agents including fentanyl, carfentanil, and as of September 2024, nitazenes.^[66][67]

Other cutting agents increasingly found in illicit supplies include the veterinary drug xylazine and the designer drugs (synthetic triazolobenzodiazepines) bromazolam, clobromazolam, phenazolam, and flualprazolam.^[68] In April 2025, U.S. Attorney General Pam Bondi stated a desire to regulate xylazine under U.S. federal drug law) as a Schedule III controlled substance.^[69] Xylazine is currently a controlled substance under state statutes in Michigan and New York.^[70]

Mandrax is the trade name of a pharmaceutical combination drug consisting of methaqualone and diphenhydramine.,^[71] once prescribed in South Africa, but banned in 1993. "Mandrax" is now synthesized via clandestine chemistry as a free base preparation, which is smoked for an intense, short-lived "high".^[72]

See also

• Codrugs
• Synergy#Drug synergy