The Competitive Marketplace

Transcription

1 The Competitive Marketplace Summary Module 1: The Acute Pain Marketplace NOTES: Marketplace Dynamics Marketplace factors that may impact acceptance of a new opioid in the marketplace include: Pain policies Fear of prescribing opioids ( opiophobia ) Ambulatory surgical centers (ASCs) Professional and advocacy organizations Pain Policies Pain policies are aimed at establishing a system of drug controls to help: Prevent abuse and diversion Regulate professional practice Improve pain management by ensuring availability of needed medications Policies exist at federal and state levels. State pain policies, if they are more restrictive, supersede federal policies. Policies vary by state: In Washington state, primary care physicians (PCPs) are limited on opioid prescribing for nonmalignant pain Selective scheduling by state Prescription quantity limitations Restrictions on samples and mail programs Regulations on use of opioids by specialty and/or diagnosis 1

2 As of June 2014, 48 states had controlled substance prescription monitoring programs, 1 state had enacted legislation but the program was not yet operational, and 1 state had legislation pending NOTES: Fear of Prescribing Opioids Among healthcare professionals, fear of prescribing opioids ( opiophobia ) is driven by: Fear of addiction Misconceptions of pain terminology Lack of widespread use of screening tools Fear of diversion Precludes validation of true pain Lack of widespread use of opioid contracts or drug screening Fear of regulatory scrutiny Concerns over loss of license Lack of familiarity with the Federation of State Medical Boards (FSMB) guidelines Fear of US Drug Enforcement Agency (DEA) investigation based on prescribing practice Pain policy knowledge gaps Evoke a more conservative approach to pain management 2

3 Ambulatory Surgical Centers (ASCs) ASCs are medical facilities that specialize in elective same day or outpatient surgical procedures but do not offer emergency care. They may be owned or operated by physicians, hospitals, or corporations (or a combination of 2 or all 3). NOTES: ASCs may constitute an expanding market for opioid analgesics. Professional Organizations Professional organizations may impact how healthcare professionals manage pain: American Academy of Pain Medicine (AAPM) Medical specialty society representing physicians practicing in the field of pain medicine Involved in education, training, advocacy, and research in pain medicine Web site: American Academy of Pain Management (AAPM) An inclusive, interdisciplinary organization of clinicians that provides education, sets standards of care, and promotes advocacy Web site: American Pain Society (APS) A multidisciplinary community that brings together a diverse group of scientists, clinicians, and other professionals to increase the knowledge of pain and transform public policy and clinical practice to reduce pain-related suffering Web site: 3

4 Advocacy Organizations Pain advocacy organizations may also impact how patients manage and cope with their pain: National Pain Foundation (NPF) A nonprofit organization established to advance functional recovery of persons in pain through information, education, and support Mission is to improve the quality of life for those living with pain through information, education, and support Provides a virtual community for pain patients, their families, and friends Web site: The following table summarizes key points you should know about the acute pain marketplace. The table lists both positive and negative marketplace dynamics. Positive Marketplace Dynamics Large prescription market Undertreatment of moderate to severe acute pain Limited promotion from competitors Despite availability of multiple products, the market looks and acts like a single-product market (eg, oxycodone-based opioid medications) Products are prescribed for pain relief across various diagnoses Key Marketplace Dynamics Negative Marketplace Dynamics Habitual prescribing of one opioid ( one-fits-all mentality) Prohibition to refill prescriptions for Schedule II Federally Controlled Substance (C-II) opioid analgesics Regulatory scrutiny on prescribers Generic nature of the marketplace Physicians are familiar, comfortable, and moderately satisfied with currently marketed products Prescription Monitoring Programs (PMPs) have physicians scared that the DEA is watching Some physicians aren t aware of the overall level of gastrointestinal (GI) side effects patients are experiencing 4

5 Physical Medicine and Rehabilitation (PM&R) Centers PM&R centers are relatively heavy prescribers of C-II short-acting opioids (SAOs). A C-II SAO that a patient starts taking at a PM&R center may be one they continue taking after discharge. NOTES: PM&R centers are hospital-like facilities that provide inpatient and/ or outpatient services for physical rehabilitation following surgery or trauma. Services may include: Physician services for the medical needs of patients Rehabilitation nursing to oversee treatment program of the patient Physical therapy to address physical function, mobility, and safety Occupational therapy to promote independence and reintegration Speech-language therapy to treat communication and swallowing disorders Case manager to coordinate the care plan with physician, caregivers, and family Post-discharge services to provide outpatient therapy and home health Key staff members affiliated with a PM&R center may include: Physiatrists: Frequently prescribe C-II SAOs for pain relief Have control of patient for longer time periods at PM&R centers than other physicians More aware of medication adverse events that could affect patient ability to participate in rehabilitation Can be influenced to reevaluate pain medication during the rehabilitation process 5

6 Surgeons: often initiate C-II opioid prescription, but only prescribe enough for transfer to inpatient rehabilitation facility NOTES: Primary care physicians: interest in reducing side effects and decreasing opioid use in the outpatient setting Nurses and physical therapists: frequent patient contact and relatively high influence on physiatrist prescribing decisions Occupational and speech therapists: occasional or infrequent patient contact and relatively low influence on physiatrist prescribing decisions PM&R center patients (admission, diagnoses, and flow) include: Joint replacement surgery, major multiple trauma, hip fracture, and burns: frequent prescriptions for C-II SAOs Spinal cord injury, arthritis, congenital deformity, and amputation: occasional prescriptions for C-II SAOs Stroke, brain injury, neurological disorder, and general postsurgical weakness: no prescriptions for C-II SAOs Patient flow and prescribing decision points: at each decision point, the patient s case is evaluated and prescriptions are continued, changed, or added Acute care hospital (ie, for surgery or stabilization of the trauma patient): initial C-II SAO prescription Inpatient PM&R center: C-II SAO reassessment Outpatient rehabilitation/home: C-II SAO final assessment Upon discharge from inpatient rehabilitation, a primary care physician, surgeon, or outpatient physiatrist assumes responsibility for continuing pain management prescription 6

7 C-II SAO Marketplace Overview C-II SAO Primary Competitors Key competitors in the acute pain marketplace are orally administered C-II SAOs. Most opioid analgesics are classified by the DEA as C-II. This means they have a high potential for abuse, which may lead to severe psychological or physical dependence. NOTES: C-II opioid analgesics may be stratified into 2 groups SAOs and longacting opioids (LAOs). SAOs are typically formulated as immediate-release tablets that provide a relatively short period of analgesia. They are usually taken several times a day. LAOs are typically formulated as controlled- or prolonged-release oral formulations that provide a relatively long period of analgesia. They are usually taken once or twice daily. You will primarily compete with the following C-II SAOs: Percocet (oxycodone; acetaminophen), other brands (Roxicet, Oxycet), and generics Roxicodone (oxycodone hydrochloride [HCl]) and generics Percodan (oxycodone; aspirin) and generics Combunox (brand discontinued) (oxycodone; ibuprofen; generics only) Dilaudid (hydromorphone HCl) and generics Vicodin (hydrocodone; acetaminophen), other brands (Norco ), and generics 7

8 C-II SAO Secondary Competitors You will also compete with the following C-II SAOs: NOTES: Morphine sulphate (generic only) Opana IR (oxymorphone) and generics Demerol (meperidine) and generics Other Marketplace C-II SAO Additionally, another marketplace C-II SAO of interest is: Levophanol tartrate However, it is not considered a direct competitor. Adjuvant Medications Because the pathophysiology of pain involves the ascending and descending pathways of the central nervous system (CNS), there are multiple strategies to treat pain beyond using only analgesics. Adjuvant medications that may be administered concurrently with opioids include (not exhaustive): Antidepressants Anticonvulsants, with a focus on alpha 2 -delta ligands Adjuvant medications aren t considered competitors because approved and off-label indications are for chronic pain conditions. 8

9 The Competitive Marketplace Summary Module 2: C-II SAO Primary and Secondary Competitors This module focuses on information about the major branded C-II SAO primary and secondary competitors. You should keep in mind, however, that most of these products are also available under various generic names, as well as alternative formulations, such as injectable, or rectally administered forms. It is also important to keep in mind that these opioid analgesics were developed at different times throughout history, and depending on the medication, are indicated for different pain severities that range from moderate to moderately severe to severe. Thus, these SAOs received their US Food and Drug Administration (FDA)-approved indications at various times as the definitions of moderate and severe pain were being refined according to various criteria. Oxycodone-Based C-II SAOs Oxycodone, which is formulated into some C-II SAOs, was originally approved by the FDA in It is a semisynthetic, pure opioid agonist. Oxycodone exerts its analgesic effects by binding to mu-opioid receptors in the CNS; it can interact with other opioid receptors at higher doses. Other effects include anxiolysis, euphoria, and feelings of relaxation. It is important to know that there is no ceiling effect to analgesia with oxycodone. That is, the analgesic effects increase as the dose is increased. Regarding analgesic potency, 15 mg to 20 mg of oxycodone is equianalgesic to about 60 mg of oral morphine, according to one source. Some oxycodone-based C-II short-acting opioids are combined with: Acetaminophen A nonopiate, nonsalicylate analgesic and antipyretic The analgesic mechanism of action of acetaminophen has not been determined Aspirin (acetylsalicylic acid) A nonopiate, nonsteroidal anti-inflammatory drug (NSAID) with antipyretic properties Aspirin works by inhibiting the production of prostaglandins, including prostaglandins involved in inflammation 9

10 Prostaglandins cause pain by stimulating muscle contractions and dilating blood vessels throughout the body Ibuprofen An NSAID with analgesic and antipyretic properties Ibuprofen is thought to work by inhibiting cyclooxygenase activity and the production of prostaglandins Ibuprofen acts on the peripheral body and does not affect opioid receptors Percocet Percocet is the major brand name for oxycodone and acetaminophen tablets. However, this combination is also available as other brand names, including Endocet and Roxicet. It is also available as a generic from a variety of companies. Percocet is formulated as tablets in the following strengths (oxycodone hydrochloride [HCl]/ acetaminophen): 2.5 mg/325 mg 5 mg/325 mg 7.5 mg/325 mg 10 mg/325 mg Indication Percocet is indicated for the relief of moderate to moderately severe pain. Dosage The Percocet dosage should be adjusted according to the severity of the pain and the response of the patient. The usual adult dosages are: Percocet 2.5 mg/325 mg: 1 or 2 tablets every 6 hours as needed for pain All other tablet strengths: 1 tablet every 6 hours as needed for pain If pain is constant, the opioid analgesic should be given at regular intervals on an around-the-clock schedule. 10

11 The total daily dose of acetaminophen should not exceed 4 g (8 500-mg tablets). Warnings The Percocet label includes a boxed warning for hepatotoxicity associated with acetaminophen overdose. Other select warnings listed in the Percocet label include: Misuse, abuse, and diversion of opioids Respiratory depression Head injury and increased intracranial pressure Hypotension Serious skin reactions Hypersensitivity/anaphylaxis Adverse Reactions Serious adverse reactions include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, and shock. The most frequent adverse reactions include lightheadedness, dizziness, drowsiness/sedation, nausea, and vomiting. Other adverse reactions include euphoria, dysphoria, constipation, and pruritus. 11

12 Roxicodone Roxicodone is the major brand name for oxycodone tablets. However, oxycodone tablets are also available as a generic from various companies. Roxicodone is formulated as tablets containing the following strengths of oxycodone hydrochloride (HCl): 5 mg 15 mg 30 mg Indication Roxicodone is indicated for the management of moderate to severe pain where the use of an opioid analgesic is appropriate. Dosage The Roxicodone dosage should be individually adjusted according to the severity of pain, patient response, and patient size. Patients who have not been receiving opioid analgesics should be started on Roxicodone in a dosing range of 5 mg to 15 mg every 4 to 6 hours as needed for pain, and the dose should be titrated based on the individual patient s response to the initial dose. For control of severe chronic pain, Roxicodone should be administered on a regularly scheduled basis, every 4 to 6 hours, at the lowest dosage level that will achieve adequate analgesia. Warnings The Roxicodone label does not have a boxed warning. Warnings listed in the Roxicodone label include: Respiratory depression Hypotensive effect Head injury and increased intracranial pressure 12

13 Adverse Reactions Serious adverse reactions include respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock. The most frequent adverse reactions include nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. Percodan Percodan is the major brand name for oxycodone and aspirin tablets. Note this combination is also available in generic form from various companies. It is formulated as tablets containing mg of oxycodone hydrochloride (HCl) and 325 mg of aspirin. Indication Percodan is indicated for the management of moderate to moderately severe pain. Dosage The Percodan dosage should be adjusted according to the pain severity and the response of the patient. The usual dosage is 1 tablet every 6 hours as needed for pain. The maximum daily dose of aspirin should not exceed 4 g (12 tablets). If the pain is constant, the opioid analgesic should be given at regular intervals on an around-theclock schedule. Warnings The Percodan label does not have a boxed warning. Warnings listed in the Percodan label include: Misuse and abuse of opioids Respiratory depression Head injury and increased intracranial pressure Hypotensive effect 13

14 Use with alcohol (increased bleeding risk while taking aspirin and heavy, chronic alcohol consumption) Coagulation abnormalities (risk associated with aspirin) GI side effects (eg, stomach pain, heartburn, nausea, vomiting, GI bleeding) Peptic ulcer disease (associated with aspirin) Adverse Reactions Serious adverse reactions include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, and shock. The most frequent adverse reactions include lightheadedness, dizziness, drowsiness/sedation, nausea, and vomiting. Other adverse reactions include euphoria, dysphoria, constipation, and pruritus. Combunox Combunox was the major brand name for oxycodone and ibuprofen tablets, though the brand has been discontinued. Generic formulations are currently available. Oxycodone and ibuprofen tablets contain 5 mg of oxycodone hydrochloride (HCl) and 400 mg of ibuprofen. Indication Oxycodone and ibuprofen tablets are indicated for the short-term (no more than 7 days) management of acute, moderate to severe pain. Dosage The dosage should not exceed 4 tablets in a 24-hour period and should not exceed 7 days. Warnings The label for oxycodone/ibuprofen tablets has boxed warnings associated with its NSAID component (ibuprofen) for the following: Cardiovascular risk and thrombotic events GI effects (ulceration, bleeding, and perforation) 14

15 Other warnings listed in the label include: Hypertension (increased incidence associated with ibuprofen) Congestive heart failure and edema (caution associated with ibuprofen) Misuse, diversion, and abuse of opioids Respiratory depression Hypotension Use in head injury and increased intracranial pressure Mask/obscure diagnosis of patients with acute abdominal conditions Anaphylactoid reactions Renal injury (risk associated with ibuprofen) and use in patients with advanced renal disease Skin reactions (risk associated with ibuprofen) Risk of congenital defect (in late pregnancy) Interactions with alcohol or drugs of abuse (additive effects on CNS) Adverse Reactions In single-dose studies, adverse reactions reported in 1% of patients who received oxycodone/ ibuprofen and at a higher incidence than placebo included nausea, somnolence, vomiting, dizziness, sweating, and flatulence. In a multiple-dose study, adverse reactions reported in 2% of patients who received oxycodone/ ibuprofen included nausea, dizziness, somnolence, headache, constipation, vomiting, asthenia, fever, vasodilation, diarrhea, and dyspepsia. 15

16 Non Oxycodone-Based C-II SAO Primary Competitors Dilaudid Dilaudid is the major brand name for hydromorphone hydrochloride (HCl). Hydromorphone was originally approved by the FDA in Hydromorphone is now available as a generic from various companies. Hydromorphone is a derivative of morphine, a pure opioid agonist with analgesic properties. It is believed to exert its analgesic effects by binding to mu-opioid receptors in the CNS. Dilaudid is formulated as: Immediate-release tablets (2 mg, 4 mg, and 8 mg) Liquid for oral administration (1 mg/ml) Indication Dilaudid is indicated for the management of pain in patients where an opioid analgesic is appropriate. Dosage The usual starting dosages are: Tablets: 2 mg to 4 mg every 4 to 6 hours Liquid: 2.5 ml to 10 ml ( mg) every 3 to 6 hours as directed by the clinical situation Equianalgesic potency (according to one source): 7.5 mg of hydromorphone is equianalgesic to 60 mg of morphine Warnings The label for Dilaudid has a boxed warning for hydromorphone as a C-II SAO with a high potential for abuse and risk of producing respiratory depression. Other warnings listed in the Dilaudid label include: Interactions with alcohol and drugs of abuse (additive effects on CNS) Neonatal withdrawal syndrome 16

17 Use in head injury and increased intracranial pressure Hypotension Sulfite sensitivity (contains a sulfite that may cause life-threatening or less severe allergic reactions) Adverse Reactions The major hazards of Dilaudid include respiratory depression and apnea. To a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest have occurred. The most frequent adverse reactions include lightheadedness, dizziness, sedation, nausea, vomiting, sweating, flushing, dysphoria, euphoria, dry mouth, and pruritus. Vicodin Vicodin is the major brand name for hydrocodone and acetaminophen tablets. However, this combination is also available as other brand names (eg, Norco ) and in generic form from various companies. Hydrocodone is a semisynthetic narcotic analgesic. The precise mechanism of action of hydrocodone and other opiates is not known, although it is believed to relate to the existence of opiate receptors in the CNS. The analgesic action of acetaminophen involves peripheral influences, but the specific mechanism is as yet undetermined. Acetaminophen inhibits prostaglandin synthetase. Vicodin is an opioid analgesic. Vicodin is formulated as: Vicodin: Tablets containing 5 mg hydrocodone bitartrate and 300 mg acetaminophen Vicodin ES: Tablets containing 7.5 mg hydrocodone bitartrate and 300 mg acetaminophen Vicodin HP: Tablets containing 10 mg hydrocodone bitartrate and 300 mg acetaminophen Indication Vicodin tablets are indicated for the relief of moderate to moderately severe pain. 17

18 Dosage Dosage should be adjusted according to the severity of the pain and the response of the patient. The usual adult dosage is as follows: Vicodin: 1 or 2 tablets every 4 to 6 hours as needed for pain; total daily dosage should not exceed 8 tablets Vicodin ES: 1 tablet every 4 to 6 hours as needed for pain; total daily dosage should not exceed 6 tablets Vicodin HP: 1 tablet every 4 to 6 hours as needed for pain; total daily dosage should not exceed 6 tablets Warnings The label for Vicodin includes a boxed warning because of the risk of hepatotoxicity associated with acetaminophen. Other warnings listed in the Vicodin prescribing information (PI) include: Serious skin reactions (associated with acetaminophen) Hypersensitivity/anaphylaxis Respiratory depression Head injury and increased intracranial pressure Acute abdominal conditions Adverse Reactions The most frequently reported adverse reactions include lightheadedness, dizziness, sedation, nausea, and vomiting. Other adverse reactions include drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, psychic dependence, mood changes, constipation, ureteral spasm, spasm of vesical sphincters, urinary retention, respiratory depression, hearing impairment or loss, skin rash, pruritus, allergic reactions, thrombocytopenia, agranulocytosis, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. 18

19 Secondary C-II SAO Competitors The secondary competitors include orally administered C-II SAOs. Morphine Sulfate Immediate-release morphine sulfate does not have a major branded product on the market. MSIR was the primary brand name, but it is no longer manufactured. However, there are several brandname oral formulations of morphine available. Morphine sulfate is an opioid agonist with analgesic properties. Morphine sulfate is relatively selective for the mu-opioid receptor, although it can interact with other opioid receptors at higher doses. The analgesic effects of morphine are thought to be mediated by activation of opioid receptors in the CNS. Morphine sulfate is formulated as: Immediate-release tablets (15 mg and 30 mg) Solution for oral administration (10 mg/5 ml and 20 mg/5 ml, and 100 mg/5 ml) Indication Morphine sulfate tablets and oral solution (10 mg/5 ml and 20 mg/5 ml) are indicated for the relief of moderate to severe acute and chronic pain where use of an opioid analgesic is appropriate. Morphine sulfate oral solution 100 mg/5 ml (20 mg/ml) is indicated for the relief of moderate to severe acute and chronic pain in opioid-tolerant patients. Morphine sulfate oral solution 100 mg/5 ml (20 mg/ml) may cause fatal respiratory depression when administered to patients not previously exposed to opioids. Patients considered to be opioid tolerant are those who are taking at least 60 mg oral morphine per day, or at least 30 mg of oral oxycodone per day, or at least 12 mg hydromorphone per day, or an equianalgesic dose of another opioid, for a week or longer. 19

20 Dosage The recommended dosages in opioid-naïve patients are: Tablets: 15 mg to 30 mg every 4 hours as needed for pain Oral solution: 10 mg to 20 mg every 4 hours as needed for pain Warnings The label for morphine sulfate tablets does not have a boxed warning. The label for morphine sulfate oral solution has a boxed warning regarding the risk of medication errors due to confusion between different concentrations and between mg and ml. Additionally, the warning states that the highest concentration (100 mg/5 ml) is indicated for opioid-tolerant patients only. Other warnings and precautions listed in the morphine sulfate labels include: Respiratory depression Misuse, abuse, and diversion of opioids Interactions with alcohol and drugs of abuse (additive effects on CNS) Use in head injury and increased intracranial pressure Hypotension GI effects Use in pancreatic/biliary tract disease Special risk groups (eg, severe renal or hepatic impairment, elderly/debilitated patients, and convulsive disorders, among others) Driving and operating machinery Adverse Reactions The most serious adverse reactions include respiratory depression, apnea, and to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest. The most frequent adverse reactions seen on initiation of therapy include constipation, nausea, and somnolence. Other commonly observed adverse reactions include lightheadedness, dizziness, sedation, vomiting, and sweating. 20

21 Opana Opana is the major brand name for oxymorphone hydrochloride (HCl). Oxymorphone was originally approved by the FDA in 1959, and Opana was approved in Opana tablets are also available as generics. Oxymorphone is a semisynthetic opioid agonist with analgesic properties. The precise mechanism of analgesia is unknown. Oxymorphone is relatively selective for the mu-opioid receptor, although it can interact with other opioid receptors at higher doses. Opana is formulated as tablets containing 5 mg or 10 mg of oxymorphone. Indication Opana is indicated for the relief of moderate to severe acute pain where the use of an opioid is appropriate. Dosage The recommended dosage for opioid-naïve patients is 10 mg to 20 mg every 4 to 6 hours depending on the initial pain intensity. Regarding equianalgesic potency, 10 mg of oxymorphone is equianalgesic to 30 mg of morphine. Warnings The label for Opana does not have a boxed warning. Warnings and precautions listed in the Opana label include: Respiratory depression Misuse, abuse, and diversion of opioids Additive CNS depressant effects Use in head injury and increased intracranial pressure Hypotension Hepatic impairment Special risk groups (eg, Addison s disease, prostatic hypertrophy, severe impairment of pulmonary or renal function, and convulsive disorders, among others) 21

22 GI effects Use in pancreatic/biliary tract disease Driving and operating machinery Adverse Reactions The most frequent adverse reactions ( 2%) include nausea, pyrexia, somnolence, vomiting, pruritus, headache, dizziness, constipation, and confusion. Demerol Demerol is the major brand name for meperidine hydrochloride (HCl). Meperidine was originally approved by the FDA in Meperidine is also available as a generic from various companies. Meperidine is a synthetic opioid agonist with analgesic properties similar to those of morphine. It exerts its analgesic effects by binding to mu- and kappa-opioid receptors in the CNS. Meperidine has a higher affinity for the kappa-receptor than morphine does. Demerol is formulated as immediate-release tablets (50 mg and 100 mg). Indication Demerol is indicated for the relief of moderate to severe pain. Dosage The usual dosage is 50 mg to 150 mg every 3 or 4 hours as needed Equianalgesic potency (according to one source): 300 mg of meperidine is equianalgesic to 60 mg of morphine Warnings The label for Demerol does not have a boxed warning. Warnings listed in the Demerol label include: C-II with an abuse liability similar to morphine Misuse, abuse, and diversion of opioids 22

23 Additive effects when used with alcohol, other opioids, or illicit drugs that cause CNS depression Use in head injury and increased intracranial pressure Respiratory conditions (caution with asthma, risk of apnea) Hypotension Use in ambulatory patients (eg, driving and operating machinery) Risk to fetal development (during pregnancy) Labor and delivery (can cause respiratory and psychophysiologic function depression in newborn) Nursing (drug appears in milk) Adverse Reactions The major hazards of Demerol include respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest. The most frequent adverse reactions include lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. 23

24 Key Information for the C-II SAO Primary and Secondary Competitors: Summary The following table summarizes key information for the C-II SAO primary and secondary competitors. In many ways, these products are more similar than they are different. However, there are some distinguishing characteristics that set certain products apart. C-II SAO Primary Competitors Competitor Indication Dosing/Equianalgesic Potency Percocet (oxycodone; acetaminophen; Endo Pharmaceuticals) Also available in other brand names and as generic from various companies Roxicodone (oxycodone; Mallinckrodt, Inc) Also available as generic from various companies Moderate to moderately severe pain Moderate to severe pain where the use of an opioid analgesic is appropriate 2.5 mg/325 mg tablets: 1 or 2 tablets every 6 hours as needed for pain All other strengths (5-10 mg oxycodone): 1 tablet every 6 hours as needed for pain Equianalgesic potency: mg of oxycodone is equianalgesic to 60 mg of morphine The dose should be individually titrated according to severity of pain, patient response, and patient size Patients who have not been receiving opioid analgesics: start in dosing range of 5-15 mg every 4 to 6 hours as needed for pain For control of severe chronic pain, administer on a regularly scheduled basis, every 4 to 6 hours, at the lowest dosage level that will achieve adequate analgesia Key Comments/Safety Issues (not exhaustive list) Boxed warning regarding hepatotoxicity because of the acetaminophen component Warnings include respiratory depression, hypotensive effect, and use in patients with head injury or increased intracranial pressure 24

25 Percodan (oxycodone; aspirin; Endo Pharmaceuticals) Also available as generic from various companies Moderate to moderately severe pain 1 tablet (4.8 mg oxycodone, 325 mg aspirin) every 6 hours as needed for pain If pain is constant, opioid analgesic should be given at regular intervals around-theclock Several warnings associated with the aspirin component: Use with alcohol (bleeding risk) Coagulation abnormalities GI events (stomach pain, heartburn, bleeding) Peptic ulcer disease Combunox (oxycodone HCl; ibuprofen; Forest Pharmaceuticals, discontinued) Combunox brand is no longer manufactured, but is available as generic from various companies Short-term (no more than 7 days) management of acute, moderate to severe pain Dosage should not exceed 4 tablets in a 24-hour period and should not exceed 7 days Boxed warning regarding cardiovascular and thrombotic events and GI risks associated with ibuprofen. Other warnings associated with the ibuprofen component: Hypertension Congestive heart failure Renal injury Skin reactions Dilaudid (hydromorphone HCl; Purdue Pharma) Also available as generic from various companies Pain in patients where an opioid analgesic is appropriate Tablets: 2-4 mg every 4-6 hours Liquid: ml every 3-6 hours, as directed by clinical situation Equianalgesic potency: 7.5 mg of hydromorphone is equianalgesic to 60 mg of morphine Boxed warning for hydromorphone being a C-II opioid agonist with a high potential for abuse and risk of respiratory depression Other warnings and adverse reactions are similar to other C-II SAOs Vicodin (hydrocodone; acetaminophen; AbbVie, Inc) Also available in other brand names and as generic from various companies Moderate to moderately severe pain Dosage (vicodin/ acetaminophen) should be adjusted according to the severity of the pain and the response of the patient Vicodin (5 mg/300 mg): 1-2 tablets every 4-6 hours as needed for pain; not to exceed 8 tablets daily Vicodin ES (7.5 mg/300 mg): 1 tablet every 4-6 hours as needed for pain; not to exceed 6 tablets daily Vicodin HP (10 mg/300 mg): 1 tablet every 4-6 hours as needed for pain; not to exceed 6 tablets daily Boxed warning regarding hepatotoxicity associated with acetaminophen Other warnings include: Serious skin reactions Hypersensitivity/ anaphylaxis Respiratory depression Head injury and increased cranial pressure Acute abdominal conditions 25

26 C-II SAO Secondary Competitors Competitor Indication Dosing/Equianalgesic Potency Morphine sulfate Opana (oxymorphone HCl; Endo Pharmaceuticals) Also available as generic from various companies Demerol (meperidine HCl; Sanofi-Aventis) Also available as generic from various companies Moderate to severe acute and chronic pain where use of an opioid analgesic is appropriate Moderate to severe acute pain where the use of an opioid is appropriate Moderate to severe pain Tablets: mg every 4 hours as needed for pain in opioidnaïve patients Oral solution: mg every 4 hours as needed for pain in opioid-naïve patients mg every 4-6 hours Equianalgesic potency: 20 mg of oxymorphone is equianalgesic to 60 mg of morphine mg every 3-4 hours as needed Equianalgesic potency: 300 mg of meperidine is equianalgesic to 60 mg of morphine Comments/Safety Issues (not exhaustive list) The MSIR brand is no longer manufactured Similar warnings and adverse reactions as other C-II SAOs Use with caution in patients with mild impairment, starting with the lowest dose and titrating slowly. Contraindicated in patients with moderate or severe hepatic impairment Similar warnings and adverse reactions as other C-II SAOs Managing the Common GI Adverse Reactions of C-II SAOs As you have learned, the key GI adverse effects associated with C-II SAOs include nausea, vomiting, and constipation. The nausea and vomiting tend to subside with time, but the constipation does not. The following tables summarize general and specific strategies for managing GI adverse effects associated with opioid analgesics. 26

27 General Management of Mu-Agonist Opioid Adverse Effects Increase the opioid dose slowly to the recommended dose If a symptom occurs, verify its cause (ie, opioid adverse effect or other cause) If an opioid-related adverse effect occurs, consider changing the dosing regimen or route of administration to achieve relatively constant blood levels Whenever possible, add or increase the dose of a nonopioid or adjuvant analgesic for opioid-sparing effect Consider switching to another opioid Add another drug that counteracts the adverse effect Treat constipation preemptively Adverse Effect Nausea and vomiting Constipation Management of Nausea, Vomiting, and Constipation Prevention and Management Consider adding an antivomiting agent such as ondansetron or granisetron If nausea is due to slowed gastric motility, consider adding metoclopramide to improve gastric motility Antihistamines or antipsychotic agents such as haloperidol or prochlorperazine (which block nausea mechanisms in the brain) may be helpful for some patients For chronic nausea, consider adding metoclopramide and/ or an antivomiting agent such as ondansetron Implement appropriate dietary changes (ie, increase fluid or fiber intake, increase physical activity) Assess regularly and use stool softeners and laxatives Assess for and treat fecal impaction if no bowel movement in a 72-hour period Try additional methods (eg, enema or mineral oil) if not impacted 27