Table 1: Key Terms
- Opioid naïve - those who have not had opioids in the last 30 days
- Opioid tolerant - someone who has taken 60 mg daily of oral morphine, 30 mg daily of oral oxycodone, or equianalgesic dosages of other opioids for at minimum one week.34
While there are many opioids, morphine is considered by many as a standard comparator for other drugs. Morphine can be given orally, rectally, intravenously, subcutaneously, or intramuscularly.
Morphine has a use for moderate to severe acute pain and chronic severe pain. It comes in multiple formulations. For acute pain, its oral and rectal formulation is dosed at 5-30 mg every 4 hours. It is available as a tablet, solution, suppository, and parenteral solution. Morphine also comes in a controlled release form, a sustained-release form, and an extended-release form.
Longer-acting formulations include:
Arymo ER and MorphaBond ER are extended-release tablets. The initial dose is 15 mg every 8 to 12 hours in those who are not opioid-tolerant or as the first opioid used. It can be titrated every 1-2 days.
Do not give Kadian for initial opioid analgesia. For non-opioid tolerant patients, 10-30 mg once a day is recommended. Higher doses are indicted for opioid-tolerant patients. Titration may be done every 1- 2 days. When converting from other forms of morphine, it may be given once or twice a day.
MS Contin is started at 15 mg every 8-12 hours, with the dosage adjusted every 1-2 days.
Morphine should not be used in those with a hypersensitivity to morphine, those with toxin-mediated diarrheal disease, and those with severe/acute asthma, paralytic ileus, or severe respiratory depression. The extended-release form should not be used in those with GI obstruction.
The extended-release forms of morphine are not interchangeable. Changing from one medication to another should be done only by those experienced in how to do this. Extreme caution should be used when using a highly concentrated solution, so overdoses do not occur.
Fentanyl can be given as an injection, transdermal patch (Duragesic®), an oral transmucosal lozenge (Actiq®), a sublingual tablet (Abstral®), a sublingual spray (Subsys®), a buccal tablet (Fentora®), a buccal film (Onsolis®) and a nasal spray (Lazanda®). The transdermal patch is used in opioid-tolerant patients with moderate to severe pain and is often started at 25 mcg per hour and changed every 72 hours.
Fentanyl can be used for multiple reasons, including premedication for surgery, general anesthesia, as an adjunct to general and regional anesthesia, and chronic pain management. The transdermal patch is indicated for around the clock pain management in those with chronic severe pain. Fentanyl transmucosal and intranasal is indicated for cancer pain.
While no official dosage adjustment recommendations exist with those with renal or hepatic impairment, those with mild to moderate renal or hepatic impairment should likely have the dose reduced by 50 percent with the patch with fentanyl use not recommended in severe renal or hepatic impairment. Transmucosal and nasal spray have no specific recommendations for dose reduction in renal or hepatic impairment.
As with most opioids, contraindications include hypersensitivity, toxin-mediated diarrheal disease, and paralytic ileus. It should not be used for short-term pain, post-operative pain, or for those who have severe respiratory disease. The transmucosal and nasal form of fentanyl are typically only used by specialists for opioid-tolerant cancer patients.
The patch form should not be exposed to external heat, as this may increase the absorption of the medication. Also, patients with a fever may notice an increase in the absorption of the medication. The patch should only be applied to intact skin, and it contains aluminum and must be removed before an MRI.
Oxycodone is a schedule II-controlled substance and is available in multiple forms.
- Immediate release is dosed 5-20 mg every 4-6 hours (lower range for opioid-naive patients).
- The controlled release tablet is indicated for those who require around the clock pain control. It is dosed 10 mg every 12 hours to start and titrated carefully. There is also an extended-release capsule, which is started at 9 mg every 12 hours.
- It also comes as an oral concentrate and oral solution.
- Oxycodone is often combined with other analgesic agents such as acetaminophen, aspirin, and ibuprofen.
Those with a creatinine clearance less than 60 mL/min should have the dose adjusted down as serum concentration of oxycodone will increase in renal insufficiency. Those with hepatic impairment should have doses reduced. The starting dose should be lowered one-third to one-half and slowly titrated up to effect.
Oxycodone is contraindicated in those with paralytic ileus, significant respiratory depression, hypercarbia, acute or severe bronchial asthma, and GI obstruction.
Caution should be used in those with biliary tract impairment, such as acute pancreatitis, as it may lead to constriction of the sphincter of Oddi. It may lead to an elevation of intracranial pressure (ICP) and should be used carefully for those with intracranial lesions, elevated ICP, or a head injury.
Hydrocodone, classified as a Schedule II Controlled Substance in October of 2014, is available as a combination pill with a non-narcotic analgesic and by itself in an extended-release form. The combination pill has a short-acting version of hydrocodone and is dosed 2.5 to 10 mg of hydrocodone every 4-6 hours as needed for moderate to severe pain.
Hydrocodone extended-release (Zohydro ER®) is typically dosed 10 mg every 12 hours in opioid-naive patients. It is used for severe pain requiring around the clock dosing of hydrocodone. The dose may be increased every 3-7 days in 10 mg increments. Hysingla ER® is dosed 20 mg once a day while increased the dose of 10-20 mg every three to five days. Vantrela ER® is also available and is initially dosed at 15 mg every 12 hours.
Those with severe hepatic impairment should start at the lowest dose and titrate up very slowly while monitoring for side effects. Caution should be used with renal impairment as plasma concentration may rise.
Contraindications to hydrocodone include paralytic ileus, severe asthma, severe respiratory depression, and hypercarbia.
As of August 18, 2014, the DEA placed tramadol into a Schedule IV of the Controlled Substance Act. It is indicated for chronic moderate-to-severe pain. For those who do not need a rapid onset of pain relief nor affected by side effects, it may be dosed at 25 mg/day and titrated up every three days to 50-100 mg every 4-6 hours to a maximum of 400 mg a day.
Tramadol also comes in an extended-release form, which is dosed 100 mg once a day and titrated by 100 mg every five days to a maximum dose of 300 mg a day.
When prescribing tramadol to older adults, use the lower end of the dosage range and titrate slowly. In those over 75 years old, 300 mg a day should not be exceeded and utilize extreme caution with the extended-release form.
In those with a creatinine clearance less than 30 mL/min, only the immediate release formulation should be used with doses of 25-100 mg split every 12 hours (maximum dose of 200 mg a day). In those with severe liver impairment, the immediate release form should not exceed a maximum of 50 mg every 12 hours.
Patients may experience withdrawal symptoms from tramadol that may include nausea, diarrhea, anxiety, pain, sweating, tremor, and rigors. Extended use of tramadol may lead to dependence, and these medications should be tapered slowly to reduce the risk of withdrawal symptoms.
Evidence shows tramadol may increase the risk of seizures. This risk increases in those who take serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, other opioids, or other drugs that lower the seizure threshold. The risk may also increase in those who have seizures or are at risk for seizures, such as those who have a CNS infection, cancer, history of head trauma, or while patients are going through drug or alcohol withdrawal.
Oxymorphone, a schedule II medication, can be given intravenously, subcutaneously, intramuscularly or orally. For acute pain, the immediate-release tablet (Opana®) is used at 5-20 mg every 4-6 hours as needed for opioid naïve patients. For those with chronic severe pain, the extended-release tablet is used (Opana ER®) and is started at 5 mg every 12 hours and may be titrated up at 5-10 mg increments every three to seven days. Caution should be used in those with a creatinine clearance less than 50 mL/minute, and the medication should not be used in moderate to severe hepatic impairment.
Hydromorphone can be given orally, rectally, subcutaneously, intramuscularly, or intravenously. The oral medication comes in standard and extended-release forms. The standard form is used for moderate to severe pain and is often dosed 2 to 4 mg tablets every 4-6 hours. The oral liquid is typically dosed 2.5 to 10 mg every 3 to 6 hours. Parental and oral doses are not equivalent. The parenteral dose is five times more potent than the oral dose. The long-acting form (Exalgo®) is used for opioid-tolerant patients who have chronic severe pain. It is dosed 8-64 mg once a day.
Methadone can be given intravenously, subcutaneously, intramuscularly, or orally. The oral dose is started in the opioid naïve patient at 2.5 every 8-12 hours. Methadone is a high-risk drug that can lead to overdose. It has a half-life of up to five days and may accumulate in the body. Methadone may also prolong the QT interval leading to cardiac arrhythmias, especially at doses higher than 120 mg a day. Methadone should be used for severe pain that has not been responsive to other agents and only by clinicians with specific training in the use of methadone. Methadone has use in the detoxification process.
Tapentadol (Nucynta®, Nucynta ER®) is used for acute moderate to severe pain and started at 50-100 mg every six hours for the immediate-release formulation. The starting dose for the extended-release tablet is 50 mg every 12 hours. For chronic pain, it is typically dosed 100-250 mg two times a day as needed. This medication is not recommended for those with severe liver or renal insufficiency. It is also indicated for diabetic peripheral neuropathy.
Propoxyphene has been taken off the US market due to a connection with fatal cardiac arrhythmias. Meperidine is not recommended as a first-line agent for chronic pain as it is associated with high rates of central nervous system toxicity.