[1][2] Side effects of pseudoephedrine include insomnia, elevated heart rate, increased blood pressure, restlessness, dizziness, anxiety, and dry mouth, among others.

[21] In addition, doses of pseudoephedrine above the normal therapeutic range have been reported to produce stimulant effects including insomnia and fatigue resistance.

[30][53][54][55] Pseudoephedrine is also available over-the-counter and prescription-only in combination with numerous other drugs, including antihistamines (acrivastine, azatadine, brompheniramine, cetirizine, chlorpheniramine, clemastine, desloratadine, dexbrompheniramine, diphenhydramine, fexofenadine, loratadine, triprolidine), analgesics (acetaminophen, codeine, hydrocodone, ibuprofen, naproxen), cough suppressants (dextromethorphan), and expectorants (guaifenesin).

[57] Common side effects with pseudoephedrine therapy may include central nervous system (CNS) stimulation, insomnia, restlessness, excitability, dizziness, and anxiety.

[18] Rarely, pseudoephedrine therapy may be associated with mydriasis (dilated pupils), hallucinations, arrhythmias, hypertension, seizures, and ischemic colitis; as well as severe skin reactions known as recurrent pseudo-scarlatina, systemic contact dermatitis, and non-pigmenting fixed drug eruption.

[1][22] A closely related sympathomimetic and decongestant, phenylpropanolamine, was withdrawn due to associations with markedly increased blood pressure and incidence of hemorrhagic stroke.

[1][22] Besides hemorrhagic stroke, myocardial infarction, coronary vasospasm, and sudden death have also rarely been reported with sympathomimetic ephedra compounds like pseudoephedrine and ephedrine.

[18][15] A 2005 meta-analysis found that pseudoephedrine at recommended doses had no meaningful effect on systolic or diastolic blood pressure in healthy individuals or people with controlled hypertension.

[62][63][64] The maximum total daily dose of pseudoephedrine is 240 mg.[1] Symptoms of overdose may include sedation, apnea, impaired concentration, cyanosis, coma, circulatory collapse, insomnia, hallucinations, tremors, convulsions, headache, dizziness, anxiety, euphoria, tinnitus, blurred vision, ataxia, chest pain, tachycardia, palpitations, increased blood pressure, decreased blood pressure, thirstiness, sweating, difficulty with urination, nausea, and vomiting.

[67][69] Pseudoephedrine is contraindicated with MAOIs like phenelzine, tranylcypromine, isocarboxazid, and moclobemide due to the potential for synergistic sympathomimetic effects and hypertensive crisis.

[67][69][68][70] Concomitant use of pseudoephedrine with other vasoconstrictors, including ergot alkaloids like ergotamine and dihydroergotamine, linezolid, oxytocin, ephedrine, phenylephrine, and bromocriptine, among others, is not recommended due to the possibility of greater increases in blood pressure and risk of hemorrhagic stroke.

[1] Sympathomimetic effects and cardiovascular risks of pseudoephedrine may also be increased with digitalis glycosides, tricyclic antidepressants, appetite suppressants, and inhalational anesthetics.

[78][25][2] Some sources state that pseudoephedrine has a mixed mechanism of action consisting of both indirect and direct effects by binding to and acting as an agonist of adrenergic receptors.

[2] Activation of β2-adrenergic receptors produces relaxation of the smooth muscle of the bronchi,[88] causing bronchial dilation and in turn decreasing congestion (although not fluid) and difficulty breathing.

[25][26] The blood-brain barrier permeability of pseudoephedrine, ephedrine, and phenylpropanolamine is reduced compared to other amphetamines due to the presence of a hydroxyl group at the β carbon which decreases their lipophilicity.

[11][1][2] Due to its methyl group at the α carbon (i.e., it is an amphetamine), pseudoephedrine is not a substrate for monoamine oxidase (MAO) and is not metabolized by this enzyme.

[108] Pseudoephedrine may be quantified in blood, plasma, or urine to monitor any possible performance-enhancing use by athletes, confirm a diagnosis of poisoning, or to assist in a medicolegal death investigation.

In this process, specialized strains of yeast (typically a variety of Candida utilis or Saccharomyces cerevisiae) are added to large vats containing water, dextrose and the enzyme pyruvate decarboxylase (such as found in beets and other plants).

[111] The bulk of pseudoephedrine is produced by commercial pharmaceutical manufacturers in India and China, where economic and industrial conditions favor its mass production for export.

[124] Thus, normal dosage of 240 mg pseudoephedrine per day can result in urine concentration levels exceeding the limit of 150 μg/mL set by WADA for about half of all users.

[1] As a result of the increasing regulatory restrictions on the sale and distribution of pseudoephedrine, pharmaceutical firms have reformulated medications to use alternative compounds, particularly phenylephrine, even though its efficacy as an oral decongestant has been demonstrated to be indistinguishable from placebo.

Internationally, pseudoephedrine is listed as a Table I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.

Near the end of the study, Health Canada issued a warning on their website stating that those who are under the age of 12, or who have heart disease and may have strokes, should avoid taking pseudoephedrine and ephedrine.

[159] Pseudoephedrine, ephedrine, and any product containing these substances, e.g. cold and flu medicines, were first classified in October 2004 as Class C Part III (partially exempted) controlled drugs, due to being the principal ingredient in methamphetamine.

[160] New Zealand Customs and police officers continued to make large interceptions of precursor substances believed to be destined for methamphetamine production.

The DEA continued to make greater progress in its attempts to control pseudoephedrine as methamphetamine production skyrocketed, becoming a serious problem in the western United States.

[169][170][171] The states of Alabama, Arizona, Arkansas, California, Colorado, Delaware, Florida, Georgia, Hawaii (as of May 1, 2009[update]) Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana (as of August 15, 2009[update]), Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska,[172] Nevada, New Jersey, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, South Dakota, Tennessee, Texas, Utah, Vermont, Virginia, Washington, West Virginia and Wisconsin have laws requiring pharmacies to sell pseudoephedrine "behind the counter".

[174][175] The state of Oregon reduced the number of methamphetamine lab seizures from 448 in 2004 (the final full year before implementation of the prescription only law)[176] to a new low of 13 in 2009.

Additionally, similar decreases in meth lab incidents were seen in surrounding states, according to the report, and meth-related deaths in Oregon have dramatically risen since 2007.

By creating a multi-state database and the ability to compare all transactions quickly, NPLEx enables pharmacies to deny purchases that would be illegal based on gram limits, age, or even to convicted meth offenders in some states.