Sprinkleinteractions

Potent CYP1A2 Inhibitors: Avoid concomitant use

CYP2D6 Substrates: Consider dose reduction with concomitant use

7.1 Drugs Having

Clinically Important Interactions with DRIZALMA SPRINKLE Table 7: Clinically Important Drug Interactions Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of SSRIs and SNRIs including duloxetine with MAOIs increases the risk of serotonin syndrome. Intervention

The use of MAOIs intended to treat psychiatric disorders with duloxetine or within 5 days of stopping treatment with duloxetine is contraindicated.

The use of duloxetine delayed-release capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated.

Starting duloxetine in a patient who is being treated with MAOIs is also contraindicated. Examples Selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, intravenous methylene blue Other Serotonergic Drugs Clinical Impact Concomitant use of duloxetine with other serotonergic drugs increases the risk of serotonin syndrome. Intervention

Patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

Monitor for symptoms of serotonin syndrome when duloxetine is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems.

Treatment with duloxetine delayed-release capsules and any concomitant serotonergic agents, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated. Examples Other SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort Inhibitors of CYP1A2 Clinical Impact Concomitant use of duloxetine with CYP1A2 inhibitors increases AUC, C max, t 1/2 of duloxetine. Intervention Avoid concomitant use of duloxetine delayed-release capsules with potent CYP1A2 inhibitors. Examples Fluvoxamine, cimetidine, ciprofloxacin, enoxacin Dual Inhibition of CYP1A2 and CYP2D6 Clinical Impact Concomitant administration of duloxetine with potent CYP1A2 inhibitors to CYP2D6 poor metabolizers results in increased AUC and C max of duloxetine. Intervention Avoid co-administration of duloxetine delayed-release capsules and potent CYP1A2 inhibitors to CYP2D6 poor metabolizers. Examples Fluvoxamine, cimetidine, ciprofloxacin, enoxacin Drugs that Interfere with Hemostasis Clinical Impact Concomitant use of duloxetine with an antiplatelet or anticoagulant drug may potentiate the risk of bleeding. Intervention Closely monitor for bleeding for patients receiving an antiplatelet or anticoagulant drug when duloxetine is initiated or discontinued [Warnings and Precaution ]. Examples NSAIDs, aspirin, warfarin Inhibitors of CYP2D6 Clinical Impact Concomitant use of duloxetine with CYP2D6 inhibitors increase AUC of duloxetine. Greater degrees of inhibition are expected with higher doses of CYP2D6 inhibitors. Intervention Exercise caution when co-administering duloxetine delayed-release capsules and potent CYP2D6 inhibitors. Examples Paroxetine, fluoxetine, quinidine Drugs Metabolized by CYP2D6 Clinical Impact Concomitant use of duloxetine increases AUC of a drug primarily metabolized by CYP2D6 which may increase the risk of toxicity of the CYP2D6 substrate drug. Intervention Monitor plasma concentrations of CYP2D6 substrate and reduce dosage of CYP2D6 substrate drug if necessary. Examples TCAs (nortriptyline, amitriptyline, imipramine, desipramine); phenothiazines (thioridazine); Type 1C antiarrhythmics (propafenone, flecainide) Drugs that Affect Gastric Acidity Clinical Impact In patients with conditions that may slow gastric emptying (e.g., some diabetics) and drugs that raise the gastrointestinal pH may lead to earlier the release of duloxetine. Intervention Use with caution. Examples Aluminum-and magnesium-containing antacids, famotidine, proton pump inhibitors Drugs Metabolized by CYP1A2 Clinical Impact Concomitant use of duloxetine with CYP1A2 substrates may increase the AUC of CYP1A2 substrate. Intervention Use with caution. Examples Theophylline, caffeine CNS Drugs Clinical Impact Concomitant use of duloxetine with other centrally acting drugs may increase the CNS effects of duloxetine. Intervention Use with caution. Examples Centrally acting CNS drugs Drugs Highly Bound to Plasma Protein Clinical Impact Concomitant use of duloxetine with highly protein bound drugs may cause increased free concentrations of the other drug, potentially resulting in adverse reactions. Intervention Use with caution. Examples Highly plasma protein binding drugs Alcohol Clinical Impact Concomitant use of duloxetine and alcohol may cause liver injury or aggravate pre-existing liver disease. Intervention Avoid use patients with chronic liver disease or heavy alcohol use.