FMCSA Educational Video Series MEDICATIONS I

1. FMCSA Educational Video SeriesMEDICATIONS I Joseph Sentef MD, MPH, MBA, MRO Chief Medical Officer

2. MEDICATIONS I This educational presentation covers cover medications with possible side effects and drug interactions that medical examiners encounter often while performing DOT driver exams. The video is intended to provide information to help apply standards in the Federal regulations or serve as a reference for medical examiners, drivers, and motor carrier safety departments. This video and its contents are strictly educational and not legally binding on medical examiners. The most current safety, diagnostic and treatment information was obtained from various evidence-based, patient-specific guidelines.

3. MEDICATIONS I The video addresses the following medications: Amphetamines Methyphenidates Modafinils Benzodiazepines Opioids Barbiturates Gabapentinoids Antihistamines 1. First-Generation 2. Second-Generation

4. AMPHETAMINES A class of central nervous system stimulants that affect chemicals in the nerves and brain, amphetamines contribute to hyperactivity and impulse control. Amphetamines generate emotional, cognitive, and physical effects, such as increased energy and focus and decreased appetite. They may be prescribed legally for the treatment of ADHD, narcolepsy, and other conditions. They are also used illegally to improve performance, weight loss, or to generate a “high.” Many amphetamines demonstrate high potential for abuse and are legally available only through a prescription. Amphetamines are a controlled substance under the Controlled Substance Act by the Drug Enforcement Administration and have been assigned Schedule II

5. AMPHETAMINES 49 CFR 391.41(b)(12) “A person is physically qualified to drive a commercial motor vehicle if that person- Does not use a controlled substance identified in 21 CFR 1308.11 Schedule I, an amphetamine, a narcotic, or any other habit forming drug. (12)(i) Does not use any drug or substance identified in 21 CFR 1308.11 Schedule I, an amphetamine, a narcotic, or any other habit-forming drug. (i) Does not use any non-Schedule I drug or substance that is identified in the other Schedules in 21 CFR part 1308 except when the use is prescribed by a licensed medical practitioner, as defined in §382.107, who is familiar with the driver’s medical history and has advised the driver that the substance will not adversely affect the driver’s ability to safely operate a commercial motor vehicle.”

6. AMPHETAMINES Known as but not limited to: amphetamine/dextroamphetamine sulfate lisdexamfetamine dimesylate Regardless of indication, amphetamines should be administered at the lowest effective dosage and dosage should be adjusted individually according to the therapeutic needs and response of the individual. Late evening doses should be avoided because of the resulting insomnia. Dosage amphetamine sulfate- 5mg to 60mg per day in divided doses Half-life* …… 9 to 14 hours lisdexamfetamine-30mg to 70mg per day Half-life* …….47 minutes The half-life is the amount of time it takes for half of the drug to be eliminated from the body. The shorter the half-life, the quicker the drug is eliminated.

7. AMPHETAMINES Side effects Common side effects include but are not limited to the following: rapid and/or irregular heartbeat, bloody/cloudy urine, painful urination, frequent urge to urinate, low back pain, anxiety, emotional lability, agitation, dizziness, nervousness, weight loss, lack or loss of strength, dry mouth, stomach pain, headache, speech disturbance, diarrhea or constipation, shortness of breath, excessive sweating, and visual disturbance Severe side effects include but are not limited to the following: dependency/abuse, psychosis, mania, aggressive behavior, myocardial infarction or sudden death, stroke, hypertension, seizures, anaphylaxis, rhabdomyolysis, and withdrawal symptoms

8. Amphetamines: Drug Interactions Amphetamines can interact with SSRI antidepressants (fluoxetine, duloxetine, escitalopram, sertraline etc.) by causing an increase in the effects and side effects of the amphetamine such as jitteriness, anxiety, nervousness, restlessness and racing thoughts. This combination can cause serotonin syndrome, a serious condition which may include confusion, hallucinations, extreme changes in blood pressure and heart rate, blurred vision, sweating, shivering, shaking, muscle spasm, and gastrointestinal symptoms along with many other symptoms Amphetamines can interact with the pain medication tramadol or the antidepressant bupropion to increase seizure risk Amphetamines can interact with alcohol to increase the risk of cardiovascular side effects such as chest pain, increased heart rate, or blood pressure changes Amphetamines can interact with thyroid medication (synthroid, levothyroxine) to increase the risk of cardiovascular side effects such as chest pain, increased heart rate, or blood pressure changes

9. METHYLPHENIDATES Known As: methylphenidate hydrochloride methylphenidate hydrochloride extended-release tablets Methylphenidates are central nervous system stimulants. They affect chemicals in the brain and nerves that contribute to hyperactivity and impulse control. Methylphenidates are used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy in adults. Dosage methylphenidate hydrochloride: 20mg to 30mg daily in divided doses. Max dose is 60mg………….Half-life* 3.5 hours methylphenidate hydrochloride extended release: 18mg or 36mg once daily………………………Half-life* 3.4 to 6.8 hours Side Effects Common side effects include but are not limited to insomnia, rapid heart rate, nausea, decreased appetite, anxiety, irritability, xerostomia, and hyperhidrosis.

10. Methylphenidates: Drug Interactions Methylphenidates can interact with the antidepressant bupropion to lower the seizure threshold and increase the risk for seizures Methylphenidates can interact with SSRI antidepressants (fluoxetine, duloxetine, escitalopram, sertraline etc.) by causing an increase in the effects and side effects of the amphetamine such as jitteriness, anxiety, nervousness, restlessness and racing thoughts. This combination can cause serotonin syndrome, a serious condition which may include confusion, hallucinations, extreme changes in blood pressure and heart rate, blurred vision, sweating, shivering, shaking, muscle spasm, and gastrointestinal symptoms along with many other symptoms Methyphenidates can interact with amphetamines to increase the risk of hypertension and tachycardia Methyphenidates with ibuprofen or pseudoephedrine may increase the risk for hypertension or CNS stimulatory effects

11. MODAFINILS Known as: modafinil armodafinil Modafinil and armodafinil are stimulant medications that promote wakefulness. They alter the natural chemicals (neurotransmitters) in the brain and are used to treat excessive sleepiness caused by sleep apnea, narcolepsy, or shift work disorder. Dosage modafinil: 200mg once daily …….Half-life* 15 hours armodafinil: 150mg daily ………...Half-life* 15 hours Side Effects Common side effects include but are not limited to as follows: anxiety, headaches, insomnia, nausea, skin rash, anorexia, and xerostomia.

12. Modafinils: Drug Interactions Modafinils can interact with methadone, hydrocodone, and oxycodone by reducing those levels in the blood thereby causing withdrawal symptoms such as watery eyes, excessive sweating, irritability, anxiety and depression, and gastroenteritis type symptoms Modafinils can increase blood levels of the proton pump inhibitor esomeprazole Modafinils should not be combined with central nervous system stimulants such as ADHD treatments like amphetamine sulfates which potentiate side effects of those drugs such as rapid and/or irregular heartbeat, bloody/cloudy urine, painful urination, frequent urge to urinate, low back pain, anxiety, weight loss, lack or loss of strength, dry mouth, and abdominal pain Modafinils can interact with caffeine to increase the risk of cardiovascular and CNS stimulatory effects Modafinils can decrease efficacy of hormonal birth control methods

13. BENZODIAZEPINES Known as: alprazolam, clonazepam, diazepam, lorazepam, temazepam, chlordiazepoxide, estazolam, clorazepate, triazolam, midazolam Benzodiazepines are a class of agents that work in the central nervous system acting on specific receptors in the brain called gamma-aminobutyric acid-A (GABA-A) receptors. Benzodiazepines attached to these receptors make the nerves in the brain less sensitive to stimulation, which has a calming effect. Benzodiazepines are used to treat alcohol withdrawal, anxiety, as a muscle relaxant, panic disorder, seizures, sleep disorders, and to induce relaxation and cause amnesia prior to surgical operations (i.e. midazolam).

14. BENZODIAZEPINES 49 CFR 391.41(b)(12) “A person is physically qualified to drive a commercial motor vehicle if that person- Does not use a controlled substance identified in 21 CFR 1308.11 Schedule I, an amphetamine, a narcotic, or any other habit forming drug. (12)(i) Does not use any drug or substance identified in 21 CFR 1308.11 Schedule I, an amphetamine, a narcotic, or any other habit-forming drug. (i) Does not use any non-Schedule I drug or substance that is identified in the other Schedules in 21 CFR part 1308 except when the use is prescribed by a licensed medical practitioner, as defined in §382.107, who is familiar with the driver’s medical history and has advised the driver that the substance will not adversely affect the driver’s ability to safely operate a commercial motor vehicle.”

15. BENZODIAZEPINES Problems arise when benzodiazepines are taken at higher doses than recommended, or when they are taken for more than 2 to 4 weeks. Benzodiazepines are potentially addictive and the risk of becoming emotionally and physically dependent on them increases with increased dosage and frequency. In addition, tolerance can develop with chronic use which could require a dosage increase for resolution of symptoms. Dosage alprazolam .25mg to .5mg up to 3 times a day Half-life*….. 6-26 hours (short-acting) clonazepam .25 to .5mg up to 2 times a day Half-life*….. 20-50 hours (long-acting) diazepam 2mg to 10mg up to 4 times daily Half-life*….. 20-100 hours (long-acting)

16. BENZODIAZEPINES Dosage: lorazepam 1mg-2mg up to 3 times daily Half-life*…..10-20 hours (medium-acting) temazepam 7.5mg -30mg once daily at bedtime Half-life*…..10-20 hours (medium-acting) chlordiazepoxide 5mg to 10mg up to 4 times daily Half-life*….. 30-100 hours (long-acting) triazolam .25mg once daily at bedtime Half-life*….. 2-5 hours (short-acting) estazolam 1mg to 2mg once daily at bedtime Half-life*……10-24 hours (medium-acting) clorazepate 15mg to 60mg in divided doses Half-life*……10-24 hours (long-acting) The half-life is the amount of time it takes for half of the drug to be eliminated from the body. The shorter the half-life, the quicker the drug is eliminated.

17. BENZODIAZEPINES Side Effects Common side effects include but are not limited to the following: drowsiness, fatigue, dizziness, headaches, ataxia (poor coordination), and depression. Other side effects may include cognitive dysfunction, memory impairment, constipation, dysarthria (motor speech), irritability, and upper respiratory symptoms The lowest possible effective dose should be prescribed. The risk of dependence may increase with dose and duration of treatment. Because of the danger of withdrawal, abrupt discontinuation of treatment should be avoided Benzodiazepines are a controlled substance under the Controlled Substance Act by the Drug Enforcement Administration and have been assigned Schedule IV

18. Benzodiazepines: Drug Interactions Benzodiazepines will interact with narcotic pain medications such as hydrocodone, oxycodone, buprenorphine, tramadol, and morphine to cause central nervous system depression causing respiratory distress, coma, and even death Benzodiazepines will interact with the antidepressant trazodone which can give increasing side effects such as dizziness, drowsiness, confusion, and difficulty concentrating Excessive use of benzodiazepines, or abrupt discontinuation following long term use may trigger seizures especially in individuals taking bupropion Using pregabalin together with a benzodiazepine can increase side effects such as dizziness, drowsiness, confusion and difficulty concentrating. Older individuals may experience impairment in thinking, judgement, and motor coordination

19. OPIOIDS Known as but not limited to: morphine, oxycodone, hydrocodone, fentanyl, buprenorphine, methadone, meperidine, opium, hydromorphone, oxymorphone, tramadol, tapentadol Narcotic analgesics are a class of medicines that are used to provide relief from moderate-to-severe acute or chronic pain. However, they have been overused, overprescribed, and misused resulting in more than 2 million individuals in the U.S. alone having a substance abuse disorder involving prescription narcotic analgesics. Narcotic analgesics work by binding to opioid receptors that controls pain, pleasurable and addictive behavior. They are more abundant in the brain and spinal cord but are also located elsewhere in the body such as the stomach and lungs. The main opioid receptor is the “mu” receptor.

20. OPIOIDS 49 CFR 391.41(b)(12) “A person is physically qualified to drive a commercial motor vehicle if that person- Does not use a controlled substance identified in 21 CFR 1308.11 Schedule I, an amphetamine, a narcotic, or any other habit forming drug. (12)(i) Does not use any drug or substance identified in 21 CFR 1308.11 Schedule I, an amphetamine, a narcotic, or any other habit-forming drug. (i) Does not use any non-Schedule I drug or substance that is identified in the other Schedules in 21 CFR part 1308 except when the use is prescribed by a licensed medical practitioner, as defined in §382.107, who is familiar with the driver’s medical history and has advised the driver that the substance will not adversely affect the driver’s ability to safely operate a commercial motor vehicle.”

21. OPIOIDS The most appropriate use of narcotic analgesics is for the relief of short-term, intense pain, such as that occurring immediately after surgery or due to a chronic medical condition. Dosage: morphine 10mg, 15mg, 30mg Half-life* …..2 to 4 hours (short-acting) oxycodone 5mg, 10mg, 15mg, 20mg, 30mg Half-life*….. 3.5 to 4 hours (short-acting) hydrocodone 5mg, 7.5mg, 10mg, 15mg Half-life* …..3.8-4.9 hours (short-acting) fentanyl transdermal 12mcg, 25mcg. 37.5mcg, 50mcg, 62.5 mcg, 75 mcg, 87.5mcg, 100mcg patch dose per hour Half-life* ….. 20-27 hours due to continued absorption from the drug depot in the skin (long-acting) The half-life is the amount of time it takes for half of the drug to be eliminated from the body. The shorter the half-life, the quicker the drug is eliminated.

22. OPIOIDS Dosage: buprenorphine 2mg, 8mg Half life* …..20-44 hours (long-acting) methadone 5mg, 10mg, 40mg Half life* …..8-59 hours (long-acting) meperidine 50mg, 100mg Half life* …..2.5-4 hours (short-acting) oxymorphone 5mg, 10mg – Extended Release up to 40mg Half life* …..7.3-11.3 hours (medium-acting) hydromorphone 2mg, 4mg, 8mg – ER 12mg, 16mg, 32mg Half life* …..2.5 hours (short-acting) tramadol 50mg ( up to 3 times daily) ER tab: 100mg-300mg Half-life* …..7.4-8.8 hours (medium acting) tapentadol 50mg, 75mg, 100mg Half-life* …..4.0-5.0 hours (short acting)

23. OPIOIDS Side Effects: Common side effects include but are not limited to: somnolence, dizziness, lightheadedness, headaches, nausea/vomiting, anxiety, confusion, abdominal pain, constipation, diaphoresis, asthenia (weakness), xerostomia, prolonged QT interval, and psychomotor impairment The lowest possible effective dose should be prescribed. The risk of dependence may increase with dose and duration of treatment. Because of the danger of withdrawal, abrupt discontinuation of treatment should be avoided. Serious side effects based on high dosage and continued use include respiratory depression, apnea, seizures, severe hypotension, and abuse dependency. Opioids are a controlled substance under the Controlled Substance Act by the Drug Enforcement Administration and have been assigned Schedule II and III (buprenorphine)

24. OPIOIDS: Drug Interactions/Cautions Concomitant opioid use with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death Hydrocodone/oxycodone/Methadone and the blood pressure medicine amlodipine may increase their opiate levels risking CNS and respiratory depression along with hypotension, psychomotor impairment, and cardiac arrhythmias Hydrocodone/oxycodone and hydrochlorothiazide may increase risk of hypotension and orthostasis Methadone/oxymorphone/hydromorphone cautions include CNS depression, delaying gastric emptying, hypotensive effects, lowering seizure threshold, and prolonged QT interval Tramadol cautions include respiratory depression, acute asthma, GI obstruction, suicidal ideation or behavior, severe hepatic impairment, sleep apnea, lowering seizure threshold, prolonged QT interval, and hypotensive effects

25. Barbiturates Known as but not limited to: secobarbital, pentobarbital, phenobarbital, butalbital Barbiturates are a class of drugs used extensively in the 1960s and 1970s as treatment for anxiety, insomnia, and seizure disorders. They are still in use for acute anesthesia, epilepsy, treatment of acute migraines or cluster headaches, and assisted suicide. Barbiturates are known as central nervous system depressants. Like benzodiazepines, they enhance the action of GABA, a neurotransmitter that inhibits the activity of nerve cells in the brain. They produce their effects by increasing the duration of the chloride ion channel opening at the GABA receptor increasing the potency of GABA which often results in increased toxicity. Barbiturates are a controlled substance under the Controlled Substance Act by the Drug Enforcement Administration and have been assigned Schedule II

26. Barbiturates Side Effects: Common side effects include but are not limited to the following: drowsiness, lethargy, somnolence, pain, swelling, hepatitis, urticaria, nausea/vomiting, porphyria exacerbation, physical dependence, necrosis, and thrombophlebitis. Severe side effects include but are not limited to the following: respiratory depression, blood dyscrasias, angioedema, withdrawal symptoms if stopped suddenly, megaloblastic anemia, and suicidality. Drug Interactions: Barbiturates given with opioids will increase the risk for profound CNS and respiratory depression, psychomotor impairment, and lower the seizure threshold increasing the risk for seizures Barbiturates given with acetaminophen may increase the risk of acetaminophen toxicity by affecting the liver metabolism

27. Barbiturates Drug Interactions: Barbiturates and first-generation antihistamines such as diphenhydramine may increase CNS and respiratory depression and psychomotor impairment Barbiturates given with amphetamines or bupropion may alter seizure control by decreasing the seizure threshold Dosage: secobarbital: 100mg Half-life* 28 hours pentobarbital: 150-200mg injectable Half-life* 15-50 hours phenobarbital: 15mg up to 100mg Half-life* 79 hours butalbital: 30mg (used in conjunction with acetaminophen or aspirin) Half-life* 35 hours The half-life is the amount of time it takes for half of the drug to be eliminated from the body. The shorter the half-life, the quicker the drug is eliminated.

28. Gabapentinoids Known as: gabapentin pregabalin Gabapentin and pregabalin are anti-epileptic drugs that affect chemicals and nerves in the body that are involved in the prevention of seizures and specific types of pain. Gabapentinoids act by inhibiting certain calcium channels. Gabapentin is also used off-label for treating neuropathic pain (such as diabetes), restless leg syndrome, anxiety, insomnia, bipolar disorder, alcohol dependence and postherpetic neuralgia pain. Dosage: gabapentin 300-1200mg, up to 3 times daily Half-life* …..5-7 hours pregabalin 25-300 mg, up to 2 or 3 times daily Half-life* …..6.3 hours

29. Gabapentinoids Side Effects: Common side effects of gabapentin include but are not limited to the following: dizziness, somnolence, ataxia, fatigue, fever, nystagmus, tremor, diplopia, headache, back pain, depression, amnesia, abnormal thinking, and amblyopia Serious reactions include but are not limited to the following: depression, suicidality, withdrawal seizures, anaphylaxis, and rhabdomyolysis Common side effects of pregabalin include but are not limited to the following: dizziness, somnolence, xerostomia, peripheral edema, blurred vision, weight gain, abnormal thinking, impaired coordination, pain, and constipation Serious side effects include but are not limited to the following: angioedema, exfoliative dermatitis, Stevens-Johnson syndrome, thrombocytopenia, rhabdomyolysis, suicidality, withdrawal symptoms and seizures

30. Gabapentinoids: Drug Interactions Drug Interactions: Gabapentinoids taken with opioids may increase the risk CNS and respiratory depression (additive effect), psychomotor impairment (additive effect) and alter seizure control Gabapentinoids taken with amphetamines may decrease the seizure threshold thereby causing seizures Gabapentinoids mixed with alcohol will increase the nervous system side effects including dizziness, drowsiness, and difficulty concentrating. Some individuals may experience impairment in thinking and judgment Antiepileptic drugs have been associated with an increased risk of suicidal thoughts or behavior in individuals taking this medication for any indication Pregabalin is a controlled substance under the Controlled Substance Act by the Drug Enforcement Administration and have been assigned Schedule IV. Gabapentin is not classified

31. Antihistamines: First-Generation First-Generation antihistamines known as but not limited to: diphenhydramine, promethazine, hydroxyzine, meclizine, and chlorpheniramine Antihistamines inhibit the effects of histamine at H1 receptors. Histamine is a physiologically active, endogenous substance that binds to and activates histamine H1 and H2 receptors in the respiratory tract (including the nose), the gastrointestinal tract, brain, skin vasculature, and the heart. The actions of histamine manifest clinically as characteristic allergic signs and symptoms that include sneezing, rhinitis, rhinorrhea, erythema, pruritis, and urticaria. First-generation antihistamines are highly lipophilic and therefore readily cross the blood-brain barrier, contributing to adverse central nervous system effects including sedation, drowsiness, and decreased cognitive processing.

32. Antihistamines: First-Generation Side Effects: Common side effects of first-generation antihistamines include but are not limited to the following: drowsiness, dizziness, headache, blurred vision, impaired coordination, hypotension, palpitations, tachycardia, diaphoresis, urinary retention, and diplopia Severe side effects of first-generation antihistamines include but are not limited to: seizures, arrhythmias, heat stroke, hemolytic anemia and various hematological disorders such as thrombocytopenia Drug Interactions: Antihistamines given with opioids may increase opiate levels, risking possible CNS and respiratory depression, and psychomotor impairment Antihistamines given with amitriptyline may increase CNS depression, psychomotor impairment, and have adverse anticholinergic effects

33. Antihistamines: First-Generation Drug Interactions: Antihistamines taken with beta blockers such as metoprolol may increase beta blocker levels resulting in hypotension, bradycardia or AV block Antihistamines taken with anti-hypertensives such as amlodipine or valsartan may increase the risk of hypotension Antihistamines taken with SSRIs, SNRIs, or antipsychotics may increase the risk for CNS depression and psychomotor impairment Promethazine taken with diuretics (HCTZ) may increase the risk of hypotension, SIADH, and hyponatremia (low sodium) Promethazine taken with metformin and other oral diabetes medications may alter glycemic control Meclizine taken with opioids may increase risk of CNS and respiratory depression, psychomotor impairment and severe constipation/paralytic ileus along with anticholinergic effects

34. Antihistamines: First-Generation Dosage: diphenhydramine 25mg, 50mg Half-life* 3.4-9.2 hours promethazine 12.5mg, 25mg, 50mg Half-life* 7-14 hours hydroxyzine 25mg, 50mg, 100mg Half-life* 20-25 hours meclizine 12.5mg, 25mg Half-life* 6 hours chlorpheniramine 4mg Half-life* 20-24 hours The half-life is the amount of time it takes for half of the drug to be eliminated from the body. The shorter the half-life, the quicker the drug is eliminated

35. Antihistamines: Second-Generation Second-Generation antihistamines known as but not limited to: loratadine, fexofenadine, cetirizine, levocetirizine, desloratadine Second-generation antihistamines were developed to decrease the adverse effects of the first-generation drugs. They have a higher specificity for binding to H1 receptors, lower affinity for non-histamine receptors, and are lipophobic (poor penetration of the blood brain barrier). These drugs are less likely to be sedating than first-generation antihistamines and they also have longer half-lives, permitting once or twice a day dosing. Third-generation antihistamines are the active enantiomer (levocetirizine) or metabolite (desloratadine and fexofenadine) derivatives of second-generation drugs created to have increased efficacy with fewer adverse drug reactions. There is some controversy with the use of the term third-generation.

36. Antihistamines: Second-Generation Side Effects: • Common side effects of second-generation antihistamines include but are not limited to: drowsiness, fatigue, abdominal pain, headache, dry mucous membranes, diarrhea, and pharyngitis • Severe side effects of second-generation antihistamines include but are not limited to: bronchospasm, hepatotoxicity, syncope, seizures, thrombocytopenia, and anaphylaxis reaction Dosage: one tablet daily • loratadine: 10mg………………………….Half-life* 28 hours • fexofenadine: 30mg, 60mg,180mg...Half-life* 14.4 hours • cetirizine: 5mg,10mg………………........Half-life* 8.3-24.9 hours • levocetirizine: 10mg………………..........Half-life* 8-9 hours • desloratadine: 5mg……………………….Half-life* 27 hours The half-life is the amount of time it takes for half of the drug to be eliminated from the body. The shorter the half-life, the quicker the drug is eliminated.

37. Educational Video Series I