Dolcet Mini Drug Interactions

MAO inhibitors (e.g. phenelzine, tranylcypromine, linezolid): Mechanism: Additive or synergistic pharmacodynamic effect.
Clinical Impact: The concomitant use of this drug with MAO inhibitors, or use within 14 days of their discontinuation, is contraindicated due to the increased risk of seizures and serotonin syndrome. (See Contraindications.) MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity.
Intervention: Do not use this drug in patents taking MAOIs or within 14 days of stopping such treatment.
Serotonergic Drugs (e.g. Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system including mirtazapine and trazadone, and some muscle relaxants such as cyclobenzaprine, metaxalone): Mechanism: Additive or synergistic pharmacodynamic effect.
Clinical Impact: Concomitant use of tramadol with serotonergic drugs increases the risk of adverse events, including seizures and serotonin syndrome.
Intervention: Use caution when administering this drug in patients taking serotonergic drugs and monitor for signs of adverse events. Discontinue this drug if serotonin syndrome is suspected.
CYP3A4 Inducers (e.g. Rifampin, carbamazepine, phenytoin): Mechanism: Enzyme induction resulting in increased rate of metabolism of tramadol.
Clinical Impact: The concomitant use of this drug and an inducer of CYP3A4 can decrease the plasma concentration of tramadol, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to tramadol.
After stopping an inducer of CYP3A4, as the effects of the inducer decline, the tramadol plasma concentration will increase, which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression, seizures and serotonin syndrome.
Intervention: If concomitant use is necessary, consider increasing the drug dosage until stable drug effects are achieved. Follow patients for signs of opioid withdrawal. If an inducer of CYP3A4 is discontinued, consider this drug dosage reduction and monitor for seizures and serotonin syndrome, and the signs of sedation and respiratory depression. In case of combined use with carbamazepine, tramadol's analgesic effect and acting time may be decreased significantly by decreased plasma concentration of tramadol. As carbamazepine increased tramadol's metabolism and may increase risk of seizures of tramadol, combined use is prohibited.
Inhibitors of CYP2D6 (e.g. Quinidine, fluoxetine, paroxetine, amitriptyline, and bupropion): Mechanism: CYP2D6 inhibition resulting in decreased rate of metabolism of tramadol.
Clinical Impact: The concomitant use of Tramadol/Paracetamol (Dolcet Mini) and CYP2D6 inhibitors may result in an increase in the plasma concentration of tramadol and a decrease in the plasma concentration of M1, particularly when an inhibitor is added after a stable dose of Tramadol/Paracetamol (Dolcet Mini) is achieved. Since M1 is a more potent μ-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome.
After stopping an inhibitor of CYP2D6, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease and the M1 plasma concentration will increase which could increase or prolong therapeutic effects but also increase adverse reactions related to opioid toxicity, and may cause potentially fatal respiratory depression.
Intervention: If concomitant use of an inhibitor of CYP2D6 is necessary, follow patients closely for adverse reactions including opioid withdrawal, seizures and serotonin syndrome. If an inhibitor of CYP2D6 is discontinued, consider lowering this drug dosage until stable drug effects are achieved. Follow patients closely for adverse events including respiratory depression and sedation.
Inhibitors of CYP3A4 (e.g. Macrolide antibiotics including erythromycin, azole-antifungal agents including ketoconazole, protease inhibitors including ritonavir): Mechanism: CYP3A4 inhibition resulting in decreased rate of metabolism of tramadol.
Clinical impact: The concomitant use of this drug and an inhibitor of CYP3A4 can increase the plasma concentration of tramadol and may result in a greater amount of metabolism via CYP2D6 and greater levels of M1. After stopping an inhibitor of CYP3A4, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease, resulting in decreased opioid efficacy and possibly signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol.
Intervention: If concomitant use is necessary, consider dosage reduction of this drug until stable drug effects are achieved. Follow patients closely for increased risk of serious adverse events including seizures and serotonin syndrome, and adverse reactions related to opioid toxicity including potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of this drug is achieved. If an inhibitor of CYP3A4 is discontinued, consider increasing the drug dosage until stable drug effects are achieved and follow patients for signs and symptoms of opioid withdrawal.
Benzodiazepines and Other Central Nervous system (CNS) Depressants including alcohol (e.g. Benzodiazepines and other sedatives/hypnotics, tranquilizers, muscle relaxants, general anesthetics, other opioids, alcohol): Mechanism: Additive or synergistic pharmacodynamic effect.
Clinical Impact: The concomitant use of tramadol with central nervous system depressants, such as benzodiazepines, alcohol, may produce additive CNS depressant effects, such as profound sedation and respiratory depression. If concomitant use of this drug with a CNS depressant is clinically necessary, prescribe the lowest effective dosages and minimum duration for both drugs and follow patients closely for signs of respiratory depression. Due to additive pharmacodynamic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation.
Warfarin: Clinical Impact: In case this drug is used in combination with warfarin-like drugs, increased coagulation time (INR) was reported, so prothrombin time shall be assessed regularly if appropriate medically. Post-marketing surveillance of tramadol has revealed rare reports of alteration of warfarin effect, including elevation of prothrombin times. There have been several reports that suggest that paracetamol may produce hypoprothrombinemia when administered with warfarin-like compounds.
Intervention: Monitor the prothrombin time of patients on warfarin for signs of an interaction and adjust the dosage of warfarin as needed.
Others: An absorption rate of paracetamol may be increased with metoclopramide or domperidone, and absorption can be reduced with cholecystyramine.
Concomitant administration of tramadol and cimetidine does not result in clinically significant changes in tramadol pharmacokinetics.