Zamadol

Action

Inhibits reuptake of serotonin and norepinephrine in CNS

Availability

Tablets: 50 mg

Tablets (extended-release): 100 mg, 200 mg, 300 mg

Tablets (orally disintegrating [ODT]): 50 mg

Indications and dosages

➣ Moderate to moderately severe pain in patients who require around-the-clock treatment of pain for an extended period

Adults: In rapid titration, 50 to 100 mg (immediate-release) P.O. q 4 to 6 hours p.r.n. (not to exceed 400 mg/day, or 300 mg/day in patients older than age 75). In gradual titration, initially 25 mg (immediate-release) P.O. daily; increase by 25 mg/day q 3 days to 100 mg/day, then increase by 50 mg/day q 3 days, up to 200 mg/day p.r.n. Alternately, 100 mg P.O (extended-release) up to a maximum of 300 mg daily. Titrate daily doses by 100-mg/day increments q 2 to 3 days (Ryzolt) or q 5 days (ConZip) to achieve a balance between adequate pain control and individual tolerability. Continue with lowest effective dose. Maximum dose is 300 mg/day. For patients on immediate-release product, calculate total 24-hour immediate-release dose and initiate at a dose rounded down to next lower 100-mg increment. Individualize dose according to patient need and tolerance, not to exceed 300 mg daily. Or, in patients not requiring rapid analgesic effect, tolerability can be improved by initiating therapy with a titration regimen. Total daily dose may be increased by 50 mg (ODT tablets) P.O. as tolerated q 3 days to reach 200 mg/day (50 mg q.i.d.). After titration, 50 to 100 mg (ODT tablets) P.O. can be administered as needed for pain relief q 4 to 6 hours, not to exceed 400 mg/day.

Dosage adjustment

• Renal or hepatic impairment

Contraindications

• Hypersensitivity to drug, its components, or opioids

• Acute intoxication with alcohol, sedative-hypnotics, centrally acting analgesics, opioid analgesics, or psychotropic agents

• Physical opioid dependence

• Significant respiratory depression, acute or severe bronchial asthma or hypercapnia in unmonitored settings or absence of resuscitative equipment

Precautions

Use cautiously in:

• seizure disorder or risk factors for seizures, increased intracranial pressure, head trauma, acute abdomen, patients at risk for respiratory depression, patients who use alcohol in excess, patients who suffer from emotional disturbance or depression, patients receiving CNS depressants, other opioids, anesthetics, tranquilizers, or sedative-hypnotics

• mild to severe hepatic impairment, and renal impairment with creatinine clearance less than 30 ml/minute

• history of sensitivity to phenylketones (avoid ODT use)

• history of opioid dependence or recent use of large opioid doses or patients who are suicidal or addiction-prone (use not recommended)

• concurrent use of monoamine oxidase (MAO) inhibitors (use with great caution)

• elderly patients

• pregnant or breastfeeding patients

• children younger than age 16 or 18 (ConZip) (safety not established, use not recommended).

Administration

• Give as prescribed, preferably before pain becomes severe.

Be aware that serious and rarely fatal anaphylactoid reactions have occurred, often following first dose.

Adverse reactions

CNS: dizziness, vertigo, headache, drowsiness, anxiety, stimulation, confusion, incoordination, euphoria, nervousness, sleep disorder, asthenia, hypertonia, seizures, suicide

CV: vasodilation

EENT: visual disturbances

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, flatulence, dry mouth, anorexia

GU: urinary retention and frequency, proteinuria, menopausal symptoms

Respiratory: respiratory depression (with large doses, concomitant anesthetic use, or alcohol ingestion), bronchospasm

Skin: pruritus, sweating, hives, angioedema, toxic epidermal necrolysis, Stevens-Johnson syndrome

Other: physical or psychological drug dependence, drug tolerance, serotonin syndrome, serious and rarely fatal anaphylactoid reactions

Interactions

Drug-drug. Anesthetics, antihistamines, CNS depressants, other opioids, psychotropic agents, sedative-hypnotics: increased risk of CNS depression

Carbamazepine: increased tramadol metabolism and decreased efficacy

Serotonergic drugs (including MAO inhibitors, selective norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, triptans), drugs that impair serotonin metabolism (including MAO inhibitors), drugs that impair tramadol metabolism (such as CYP2D6 and CYP3A4 inhibitors): increased risk of serotonin syndrome and seizures

Drug-diagnostic tests. Creatinine, hepatic enzymes: increased levels

Hemoglobin: decreased level

Drug-herbs. Chamomile, hops, kava, skullcap, valerian: increased CNS depression

Drug-behaviors. Alcohol use: increased CNS depression

Patient monitoring

• Assess patient's response to drug 30 minutes after administration.

• Monitor respiratory status. Withhold drug and contact prescriber if respirations become shallow or slower than 12 breaths/minute.

• Monitor for physical and psychological drug dependence. Report signs to prescriber.

Monitor patient for signs and symptoms of potentially life-threatening serotonin syndrome, which may range from shivering and diarrhea to muscle rigidity, fever, mental-status changes, and seizures.

Patient teaching

• Tell patient drug works best when taken before pain becomes severe.

• Tell patient to take extended-release tablets with or without food, to swallow them whole at same time each day with a sufficient quantity of liquid, and not to split, chew, dissolve, or crush them.

• Instruct patient to open ODT tablet blister pack and to peel back the foil on the blister; caution patient not to push tablet through foil. Instruct patient to remove a tablet and place it in the mouth, where it will dissolve in seconds and then be swallowed with saliva. Tell patient not to chew, break, or split tablet. Inform patient who has phenylketonuria that ODT tablet contains phenylalanine.

• Inform patient (and significant other as appropriate) that drug may cause respiratory depression if used with alcohol. Recommend abstinence.

Instruct patient to immediately report seizure, suicidal behavior, or suicidal ideation.

Instruct patient to watch for and immediately report signs and symptoms of serotonin syndrome (shivering and diarrhea, muscle rigidity, fever, and seizures).

Tell patient to immediately report sign and symptoms of allergic reaction (such as itching, hives, difficulty breathing, or swelling of face, tongue, or throat).

• Tell patient drug interacts with many common over-the-counter drugs and herbal remedies. Instruct him to consult prescriber before taking these products.

• Inform patient that drug can cause physical and psychological dependence. Urge him to take it only as prescribed and needed.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Caution patient to avoid alcohol use while taking this drug.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.