Duloxetine hydrochloride

Duloxetine hydrochloride.

Other drugs that may affect duloxetine The metabolism of duloxetine is related to CYP1A2 and CYP2D6. 1. CYP1A2 inhibitors - When duloxetine was co-administered with fluvoxamine (a strong CYP1A2 inhibitor) in male subjects (n=14), duloxetine AUC increased by more than 5 times, Cmax increased by about 2.5 times, and Cmax increased by 3 times. Other drugs that inhibit CYP1A2 metabolism include: cimiptine, quinolone antibiotics such as ciprofloxacin and enoxacin. 2. CYP2D6 inhibitors - Since CYP2D6 is involved in the metabolism of duloxetine, the drug concentration of duloxetine hydrochloride will increase when duloxetine and a strong CYP2D6 inhibitor are used in combination (see drug interactions under [Precautions]). Studies on combined use of benzodioxetines 1. Lorazepam - When steady-state concentrations of duloxetine (60 mg Q12 hrs) are co-administered with lorazepam (2 mg Q12 hrs), the pharmacokinetics of duloxetine are not affected by the co-administration. 2. Temazepam = When steady-state duloxetine (60 mg qhs) is co-administered with temazepam (30 mg qhs), the pharmacokinetics of duloxetine are not affected by the co-administration. Other drugs that may be affected by duloxetine 1. Drugs metabolized by CYP1A2 - In vitro drug interaction studies have shown that duloxetine has no induction effect on CYP1A2 activity. Therefore, although clinical studies on enzyme induction have not been conducted, it is not expected that the metabolism of CYP1A2 substrates (such as theophylline, caffeine) will be increased due to enzyme induction. Although in vitro studies have shown that duloxetine is a CYP1A2 inhibitor, the pharmacokinetics of theophylline did not change significantly when duloxetine (60 mg twice daily) was co-administered with theophylline, a CYP1A2 substrate. Therefore, duloxetine is unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates. 2. Drugs metabolized by CYP2D6 - Duloxetine is a moderate inhibitor of CYP2D6 and can increase the AUC and Cmax of drugs metabolized by CYP2D6. ([Precautions]), so caution should be exercised when duloxetine is co-administered with other drugs that are primarily metabolized by this enzyme and have a narrow therapeutic dose range (see drug interactions under [Precautions]). 3. Drugs metabolized by CYP2C9 - In vitro studies have shown that duloxetine has no inhibitory effect on the activity of the CYP2C9 enzyme. Therefore, although relevant clinical studies have not been conducted, it is expected that duloxetine has no inhibitory effect on the metabolism of CYP2C9 enzyme substrates. 4. Drugs metabolized by CYP3A - In vitro study results showed that duloxetine had no inhibitory or inductive effect on the activity of CYP3A enzymes. Therefore, although relevant clinical studies have not been conducted, it is expected that CYP3A enzyme substrates (such as oral contraceptives and other steroidal drugs) will not have enhanced or inhibited metabolism due to enzyme induction or inhibition. 5. Drugs metabolized by CYP2C19 - In vitro study results showed that therapeutic concentrations of duloxetine had no inhibitory effect on CYP2C19 enzyme activity. Therefore, although relevant clinical studies have not been conducted, it is expected that duloxetine has no inhibitory effect on the metabolism of CYP2C19 enzyme substrates. Studies on the combined use of benzodiazepines 6. Lorazepam - When steady-state concentrations of duloxetine (60 mg Q12hrs) are co-administered with lorazepam (2 mg Q12hrs), the pharmacokinetics of lorazepam are not affected by the combined treatment. 7. Temazepam - When steady-state concentrations of duloxetine (20 mg qhs) are co-administered with temazepam (30 mg qhs), the pharmacokinetics of temazepam are not affected by the combined treatment. 8. Highly plasma protein bound drugs - Because duloxetine is highly bound to plasma proteins, patients receiving other therapies that are highly plasma protein bound may experience increased free concentrations of other drugs when taking duloxetine, which may lead to adverse drug reactions. 9. Central nervous system drugs - Duloxetine should be used with caution when used with other centrally acting drugs, especially those with similar mechanisms of action (including alcohol). Co-administration with serotonergic drugs (e.gSNRIs, selective serotonin reuptake inhibitors, amitriptyline, tramadol) may cause serotonergic syndrome.

Duloxetine hydrochloride.

Other drugs that may affect duloxetine The metabolism of duloxetine is related to CYP1A2 and CYP2D6. 1. CYP1A2 inhibitors - When duloxetine was co-administered with fluvoxamine (a strong CYP1A2 inhibitor) in male subjects (n=14), duloxetine AUC increased by more than 5 times, Cmax increased by about 2.5 times, and Cmax increased by 3 times. Other drugs that inhibit CYP1A2 metabolism include: cimiptine, quinolone antibiotics such as ciprofloxacin and enoxacin. 2. CYP2D6 inhibitors - Since CYP2D6 is involved in the metabolism of duloxetine, the drug concentration of duloxetine hydrochloride will increase when duloxetine and a strong CYP2D6 inhibitor are used in combination (see drug interactions under [Precautions]). Studies on combined use of benzodioxetines 1. Lorazepam - When steady-state concentrations of duloxetine (60 mg Q12 hrs) are co-administered with lorazepam (2 mg Q12 hrs), the pharmacokinetics of duloxetine are not affected by the co-administration. 2. Temazepam = When steady-state duloxetine (60 mg qhs) is co-administered with temazepam (30 mg qhs), the pharmacokinetics of duloxetine are not affected by the co-administration. Other drugs that may be affected by duloxetine 1. Drugs metabolized by CYP1A2 - In vitro drug interaction studies have shown that duloxetine has no induction effect on CYP1A2 activity. Therefore, although clinical studies on enzyme induction have not been conducted, it is not expected that the metabolism of CYP1A2 substrates (such as theophylline, caffeine) will be increased due to enzyme induction. Although in vitro studies have shown that duloxetine is a CYP1A2 inhibitor, the pharmacokinetics of theophylline did not change significantly when duloxetine (60 mg twice daily) was co-administered with theophylline, a CYP1A2 substrate. Therefore, duloxetine is unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates. 2. Drugs metabolized by CYP2D6 - Duloxetine is a moderate inhibitor of CYP2D6 and can increase the AUC and Cmax of drugs metabolized by CYP2D6. ([Precautions]), so caution should be exercised when duloxetine is co-administered with other drugs that are primarily metabolized by this enzyme and have a narrow therapeutic dose range (see drug interactions under [Precautions]). 3. Drugs metabolized by CYP2C9 - In vitro studies have shown that duloxetine has no inhibitory effect on the activity of the CYP2C9 enzyme. Therefore, although relevant clinical studies have not been conducted, it is expected that duloxetine has no inhibitory effect on the metabolism of CYP2C9 enzyme substrates. 4. Drugs metabolized by CYP3A - In vitro study results showed that duloxetine had no inhibitory or inductive effect on the activity of CYP3A enzymes. Therefore, although relevant clinical studies have not been conducted, it is expected that CYP3A enzyme substrates (such as oral contraceptives and other steroidal drugs) will not have enhanced or inhibited metabolism due to enzyme induction or inhibition. 5. Drugs metabolized by CYP2C19 - In vitro study results showed that therapeutic concentrations of duloxetine had no inhibitory effect on CYP2C19 enzyme activity. Therefore, although relevant clinical studies have not been conducted, it is expected that duloxetine has no inhibitory effect on the metabolism of CYP2C19 enzyme substrates. Studies on the combined use of benzodiazepines 6. Lorazepam - When steady-state concentrations of duloxetine (60 mg Q12hrs) are co-administered with lorazepam (2 mg Q12hrs), the pharmacokinetics of lorazepam are not affected by the combined treatment. 7. Temazepam - When steady-state concentrations of duloxetine (20 mg qhs) are co-administered with temazepam (30 mg qhs), the pharmacokinetics of temazepam are not affected by the combined treatment. 8. Highly plasma protein bound drugs - Because duloxetine is highly bound to plasma proteins, patients receiving other therapies that are highly plasma protein bound may experience increased free concentrations of other drugs when taking duloxetine, which may lead to adverse drug reactions. 9. Central nervous system drugs - Duloxetine should be used with caution when used with other centrally acting drugs, especially those with similar mechanisms of action (including alcohol). Co-administration with serotonergic drugs (e.gSNRIs, selective serotonin reuptake inhibitors, amitriptyline, tramadol) may cause serotonergic syndrome.