Celecoxib-Tramadol

Celecoxib-Tramadol is a combination medication used to relieve acute pain. 

• Celecoxib-Tramadol is available under the following different brand names: Seglentis 

Common side effects of Celecoxib-Tramadol include:

• Constipation,
• Nausea,
• Sleepiness,
• Vomiting,
• Tiredness,
• Headache,
• Dizziness, and
• Abdominal pain

Serious side effects of Celecoxib-Tramadol include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• New or worsening high blood pressure,
• Heart failure,
• Liver failure,
• Low red blood cells (anemia),
• Life-threatening skin reactions,
• Stomach pain,
• Constipation,
• Diarrhoea,
• Gas,
• Heartburn,
• Nausea,
• Vomiting, 
• Dizziness,
• Tiredness,
• Weakness,
• Itching,
• Yellowing of the skin or eyes (jaundice),
• Vomit that looks like coffee grounds,
• Black or tar-like stools,
• Weight gain,
• Skin rash,
• Blistering of the skin with fever, and
• Swelling of the arms, legs, hands, and feet

Rare side effects of Celecoxib-Tramadol include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablets, Schedule IV

• 56 mg/44 mg
• 44 mg tramadol HCl equivalent to 39 mg tramadol

Acute Pain

Adult dosage

• 2 tablets (112 mg celecoxib/88 mg tramadol HCl) orally every 12 hours or as needed
• Do NOT exceed recommended dose

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Celecoxib-Tramadol has severe interactions with the following drugs:
  • alvimopan
  • procarbazine
  • rasagiline
  • safinamide
  • selegiline
• Celecoxib-Tramadol has serious interactions with at least 88 other drugs.
• Celecoxib-Tramadol has moderate interactions with at least 515 other drugs.
• Celecoxib-Tramadol has minor interactions with at least 138 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Children aged below 12 years
• Postoperative management in children aged below 18 years following tonsillectomy and/or adenoidectomy
• Significant respiratory depression
• In the setting of coronary artery bypass graft (CABG) surgery
• Severe or acute bronchial asthma in an unmonitored setting or absence of resuscitative equipment
• Known or suspected GI obstruction, including paralytic ileus
• Hypersensitivity (. g, anaphylaxis, serious skin reactions) to tramadol, opioids, celecoxib, sulfonamides, or any other component of a product
• Concurrent use of MAOIs or use within the last 14 days
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs

Effects of drug abuse

• Overdose
• Death

Short-Term Effects

• See “What Are Side Effects Associated with Using Celecoxib-Tramadol?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Celecoxib-Tramadol?”

Cautions

• Schedule IV controlled substance (. e., tramadol); exposes users to risks of addiction, abuse, and misuse
• Serotonin syndrome may occur; may be life-threatening; may occur with the use of tramadol alone, with concomitant use of serotonergic drugs, or with drugs that impair the metabolism of serotonin or tramadol
• May be subject to the same polymorphic metabolism as codeine, with ultra-rapid metabolizers of CYP2D6 substrates being potentially exposed to life-threatening levels of O-dimethyl tramadol (M1)
• Opioids can cause sleep-related breathing disorders including central sleep apnea and sleep-related hypoxemia
• Prolonged use during pregnancy can result in withdrawal in the neonate
• Seizures reported; may occur at recommended tramadol dose; coadministration with other drugs may increase seizure risk; the risk may increase in patients with epilepsy, a history of seizures, and in patients with a recognized risk for seizures
• May increase the risk of suicide; do not prescribe for patients who are suicidal or addiction-prone
• Cases of adrenal insufficiency reported with opioid use, more often following the above1 month of use; if diagnosed, treat with physiologic replacement doses of corticosteroids
• Patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, are at increased risk of the decreased respiratory drive including apnea; closely monitor
• Severe hypotension (. g, orthostatic hypotension, syncope) may occur; monitor for signs of hypotension after initiating or titrating
• May reduce respiratory drive, and resultant carbon dioxide retention can further increase intracranial pressure (ICP) in patients with increased ICP, brain tumors, head injury, or impaired consciousness; monitor for signs of sedation and respiratory depression, particularly when initiating therapy; avoid use in patients with impaired consciousness or coma
• Spasm of the sphincter of Oddi reported; opioids may cause increases in serum amylase; monitor with biliary tract disease, including acute pancreatitis, for worsening symptoms
• Serious and rarely fatal anaphylactic reactions reported
• Avoid use in patients with severe heart failure (HF) unless the benefits outweigh the risk of worsening HF; if used in such patients, monitor for signs of worsening HF
• Fluid retention and edema may occur; use of celecoxib may blunt the cardiovascular (CV) effects of several therapeutic agents used to treat these medical conditions (. g, diuretics, angiotensin-converting enzyme [ACE] inhibitors, or angiotensin-receptor blockers [ARBs])
• Long-term NSAID use may result in renal papillary necrosis and another renal injury; patients at greatest risk include elderly individuals, those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion, and those taking diuretics, ACE inhibitors, or ARBs; correct volume status in dehydrated or hypovolemic patients before initiating therapy; monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use
• Increase risk of hyperkalemia may occur; monitor potassium closely
• When used in patients with preexisting asthma (without known aspirin sensitivity), monitor for changes in signs and symptoms of asthma
• Avoid the use of NSAIDs in pregnant females at about above 30 weeks of gestation
• Use of NSAIDs at about above 20 weeks’ gestation in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
• Anemia reported in NSAID-treated patients; if any signs or symptoms of anemia occur, monitor hemoglobin or hematocrit
• NSAIDs may increase the risk of bleeding events; comorbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (. g, aspirin), serotonin reuptake inhibitors (Serotonin-norepinephrine epinephrine reuptake inhibitors (SNRIs) may increase this risk; monitor for signs of bleeding
• Do not abruptly discontinue therapy in a patient physically dependent on opioids, gradually taper the dose
• May impair the mental or physical abilities needed to perform potentially hazardous activities; warn patients not to drive or operate dangerous machinery unless tolerant to the drug effects and know the reaction to therapy
• Pharmacological activity in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections
• Hyponatremia reported, many cases severe; most cases occurred in females above 65 years and within the first week of therapy; monitor for signs and symptoms of hyponatremia (. g, confusion, disorientation) during treatment, especially during initiation of therapy; if signs and symptoms of hyponatremia are present, initiate appropriate treatment (. g, fluid restriction) and discontinue therapy
• Cases of tramadol-associated hypoglycemia reported, some resulting in hospitalization; in most cases, patients had predisposing risk factors (. g, diabetes); if hypoglycemia is suspected, monitor blood glucose levels, and consider drug discontinuation as appropriate
• Prolonged use during pregnancy can result in withdrawal in the neonate; observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly
• CV thrombotic events
  • Increased risk of serious CV thrombotic events, including myocardial infarction (MI) and stroke; use for the shortest duration possible to minimize potential risks
  • Monitor for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms
  • Inform patients about the symptoms of serious CV events and the steps to take if they occur
  • Patients treated with NSAIDs in the post-MI period reported having an increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment
  • Avoid use with recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events
  • Monitor for signs of cardiac ischemia if used in patients with a recent MI
• GI, ulceration, perforation
  • Risk factors for GI bleeding, ulceration, and perforation
  • Prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs
• Other
  • Patients treated with NSAIDs include longer duration of NSAID therapy
  • Coadministration of oral corticosteroids, aspirin, anticoagulants, or SSRI
  • Smoking
  • Alcohol use
  • Older age
  • Poor general health status
  • Elderly or debilitated patients
  • Patients with advanced liver disease and/or coagulopathy
  • Strategies to minimize the GI risk in NSAID-treated patients
  • Use the lowest effective dosage for the shortest possible duration
  • Do not use more than 1 NSAID at a time
  • Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding
  • Consider alternants for high-risk patients, as well as those with active GI bleeding
  • Monitor for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
  • If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue therapy until a serious GI adverse event is ruled out
  • In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, closely monitor for evidence of GI bleeding
• Respiratory depression
  • Serious, life-threatening, or fatal respiratory depression reported
  • May lead to respiratory arrest and death if respiratory depression is left untreated
  • Risk is greatest during the initiation of therapy; closely monitor for respiratory depression, especially within the first 24-72 hr of initiating therapy
  • Management of respiratory depression includes close observation, supportive measures, and use of opioid antagonists, depending on clinical status
  • Ultra-rapid metabolism of tramadol and other risk factors for life-threatening respiratory depression in children
  • Life-threatening respiratory depression and death have occurred in children who received tramadol
  • Tramadol may vary in metabolism based on CYP2D6 genotype, which potentially may increase exposure to an active metabolite
  • Post-marketing reports reported children aged below 12 years treated with tramadol may be more susceptible to respiratory depressant effects of tramadol
  • Children with obstructive sleep apnea who are treated with opioids for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to these respiratory depressant effects
  • Avoid use in adolescents aged 12-18 years who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks
  • Choose the lowest effective dose for the shortest period; consult patients and caregivers about these risks and the signs of opioid overdose
  • Opioid analgesic risk evaluation and mitigation strategy (REMS)
  • Opioid analgesics require a REMS program
  • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the Patient Counselling Guide (PCG)
  • Emphasize to patients and their caregivers the importance of reading the Medication Guide received from the pharmacy every time an opioid analgesic is dispensed
  • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
  • To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint
  • Patient access to naloxone for emergency treatment of opioid overdose H4
  • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
  • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
  • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose
• Hepatoxicity
  • Elevated ALT/AST reported within 2 months after initiating therapy; may occur at any time
  • Inform patients of warning signs and symptoms of hepatotoxicity
  • If signs and symptoms consistent with liver disease develop, discontinue immediately, and evaluate patient
• Hypertension
  • NSAIDs can lead to new onset of hypertension or worsening of pre-existing hypertension, which may contribute to the increased incidence of CV events
  • Caution in patients with hypertension
  • Closely monitor blood pressure during initiation and therapy
  • Patients taking ACE inhibitors, thiazides, or loop diuretics may have impaired response to these therapies when taking NSAIDs
• Serious skin reactions
  • Serious skin reactions have occurred following treatment with celecoxib, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis
• DRESS
  • Reported DRES’s events have been fatal or life-threatening; DRESS may present with fever, rash, lymphadenopathy, and/or facial swelling
  • Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis
  • Eosinophilia is often present; disorder varies in presentation; other organ systems not noted here may be involved
  • Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident; if such signs or symptoms are present, discontinue therapy and evaluate the patient immediately
• Drug interaction overview
  • Celecoxib: CYP2C9 substrate; CYP2D6 inhibitor
  • Tramadol: Substrate of CYP2B6, CYP2D6, CYP3A4
  • CYP2D6 inhibitors
    • If concomitant use of a CYP2D6 inhibitor is necessary, closely monitor for adverse reactions including opioid withdrawal, seizures, and serotonin syndrome; once the CYP2D6 inhibitor is discontinued, closely monitor for adverse events including respiratory depression and sedation
    • CYP2D6 inhibitors (. g, amiodarone, quinidine) may increase tramadol plasma levels and decrease levels of the active metabolite, M1
  • CYP2D6 substrates
    • Closely monitor for adverse events of that CYP2D6 substrate drug; evaluate patient's medical history when considering therapy
    • Celecoxib may increase levels and toxicities of CYP2D6 substrates
  • CYP3A4 inhibitors
    • Closely monitor for seizures and serotonin syndrome, and signs of respiratory depression and sedation, at frequent intervals; once the CYP3A4 inhibitor is discontinued, monitor for efficacy and signs and symptoms of opioid withdrawal
    • CYP3A4 inhibitors can increase the plasma concentration of tramadol and may increase the metabolism via CYP2D6 and greater levels of M1
  • CYP3A4 inducers
    • Closely monitor for efficacy and signs of opioid withdrawal
    • If a CYP3A4 inducer is discontinued, monitor for seizures and serotonin syndrome, and signs of sedation and respiratory depression
    • Carbamazepine, a CYP3A4 inducer, may have a significantly reduced analgesic effect of tramadol; coadministration with carbamazepine is not recommended.
    • CYP3A4 inducers can decrease the plasma concentration of tramadol, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed a physical dependence on tramadol
  • CYP2C9 inhibitors
    • Monitor for toxicities
    • CYP2C9 inhibitors may enhance the exposure and toxicity of celecoxib
  • CYP2C9 inducers
    • Monitor for efficacy maintenance
    • CYP2C9 inducers may decrease celecoxib efficacy
  • Drugs that interfere with hemostasis
    • Monitor if coadministered with anticoagulants (. g, warfarin), antiplatelet agents (. g, aspirin), SSRIs, and SNRIs for signs of bleeding
    • Monitor the prothrombin time of patients on warfarin for signs of an interaction and adjust dosage accordingly
    • Celecoxib and anticoagulants have a synergistic effect on bleeding
    • Serotonin release by platelets plays an important role in hemostasis; concomitant use of drugs that interfere with serotonin reuptake and NSAIDs may potentiate the risk of bleeding
  • Aspirin
    • Not recommended
    • If the use of low-dose aspirin for cardiac prophylaxis is necessary, monitor closely for evidence of GI bleeding
    • Coadministration of NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions
  • NSAIDs and salicylates
    • Not recommended
    • Celecoxib with other NSAIDs or salicylates (. g, diflunisal) increases the risk of GI toxicity, with little or no increase in efficacy
  • CNS depressants
    • Closely monitor for signs and symptoms of respiratory depression and sedation
    • If concomitant use with a benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
    • Coadministration of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
    • Reduce the initial dose of the opioid analgesic, and titrate based on the clinical response if initiating an opioid analgesic in a patient currently taking a benzodiazepine or other CNS depressant
    • Owing to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for emergency treatment of opioid overdose
  • Serotonergic drugs
    • Coadministration with serotonergic drugs may increase the risk for serotonin syndrome
    • Serotonergic drugs include SSRIs, SNRIs, tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (. g, mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAOIs)
  • MAOIs
    • Use in patients taking MAOIs or within 14 days of stopping such treatment is contraindicated
    • MAOI may increase the risk of serotonin syndrome or opioid toxicity (. g, respiratory depression, coma)
    • Mixed agonist/antagonist and partial agonist opioid analgesics
    • Avoid coadministration
    • May reduce the analgesic effect of tramadol or precipitate withdrawal symptoms
  • ACE inhibitors, ARBs, beta-blockers
    • NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, or beta-blockers
    • In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, coadministration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible
    • If coadministered, patients should be well hydrated; monitor for signs of worsening renal function
  • Muscle relaxants
    • Monitor for signs of respiratory depression
    • Tramadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression
  • Diuretics
    • NSAIDs may reduce the natriuretic effect of loop and thiazide diuretics
    • This effect is attributed to the NSAID inhibition of renal prostaglandin synthesis
  • Digoxin
    • Monitor digoxin levels
    • Coadministration increases digoxin serum concentration and prolongs digoxin half-life
  • Anticholinergic drugs
    • Monitor for signs of urinary retention or reduced gastric motility
    • Anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus
  • Lithium
    • Monitor for lithium toxicity
    • NSAIDs elevate plasma lithium levels and reduce renal lithium clearance
    • Mean minimum lithium concentration increased by 15%; renal clearance decreased by approximately 20%
    • Effect attributed to NSAID inhibition of renal prostaglandin synthesis
  • Corticosteroids
    • Monitor for signs of bleeding
    • Corticosteroids with celecoxib may increase the risk of GI ulceration or bleeding
  • Methotrexate
    • Monitor for toxicity
    • Coadministration of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (. g, neutropenia, thrombocytopenia, renal dysfunction)
  • Cyclosporine
    • Monitor for worsening renal function
    • Coadministration may increase nephrotoxicity
  • Pemetrexed
    • Monitor for myelosuppression, renal toxicity, and GI toxicity in patients who are impaired (CrCl 45-79 mL/min)
    • Avoid NSAIDs with short elimination half-lives (. g, diclofenac, indomethacin) for 2 days before, the day of, and 2 days following pemetrexed administration
    • Patients taking NSAIDs with longer half-lives (. g, meloxicam, nabumetone) should interrupt dosing for at least 5 days before, the day of, and 2 days following pemetrexed administration
    • Celecoxib may increase the risk of pemetrexed-associated myelosuppression, renal toxicity, and GI toxicity

Pregnancy and Lactation

• There are no available data on use in pregnant females
• Tramadol
  • Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome
  • Insufficient data are available in pregnant females to inform a drug-associated risk for major birth defects and miscarriage; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly
• Labor and delivery
  • Use of tramadol during labor may lead to respiratory depression in the neonate
  • Opioids cross the placenta and may produce respiratory depression and psychophysiological effects in neonates
  • An opioid antagonist (. g, naloxone) must be available for the reversal of opioid-induced respiratory depression in the neonate
  • Use is not recommended in pregnant females during or immediately before labor when other analgesic techniques are more appropriate
  • Opioid analgesics can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions
• Celecoxib
  • There are no adequate and well-controlled studies on pregnant females; data from observational studies regarding potential embryofoetal risks of NSAIDs during the 1st or 2nd trimesters are inconclusive
• Fetal toxicity
  • Use of NSAIDs can cause premature closure of fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment; limit dose and duration of use between about 20 and 30 weeks of gestation, and avoid use at about 30 weeks of gestation and later in pregnancy
  • Use of NSAIDs at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of fetal ductus arteriosus
  • Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
  • If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit use to the lowest effective dose and shortest duration possible; if treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios; if oligohydramnios occurs, discontinue the drug, and follow up according to clinical practice
• Labor or delivery
  • There are no studies on the effects of celecoxib during labor or delivery
  • In animal studies, NSAIDs inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth
• Infertility
  • Published animal studies have shown that the administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation
  • Consider withdrawal of NSAIDs in females who have difficulties conceiving or who are undergoing investigation of infertility
• Lactation
  • Not recommended for obstetrical preoperative medication or postdelivery analgesia in lactating women
• Celecoxib
  • Limited data from 12 breastfeeding women showed low levels of celecoxib in breast milk
  • Calculated average daily infant dose was 10-40 mcg/kg/day, below 1% of the weight-based therapeutic dose for a 2-year-old child
• Tramadol
• Safety of tramadol in infants and newborns has not been studied
  • Tramadol and its active metabolite, O-dimethyl tramadol (M1), are present in human milk
  • Published studies and cases reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk
  • Women who are ultra-rapid metabolizers of tramadol achieve higher than expected serum levels of opioids, potentially leading to higher levels of M1 in breast milk that can be dangerous in their breastfed infants
  • In women with normal tramadol metabolism (normal CYP2D6 activity), the amount of tramadol secreted into human milk is low and dose-dependent
  • Breastfeeding is not recommended during treatment