Multaq (Dronedarone) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Dronedarone is metabolized primarily by CYP 3A and is a moderate inhibitor of CYP 3A and CYP 2D6 [see Clinical Pharmacology ]. Dronedarone's blood levels can therefore be affected by inhibitors and inducers of CYP 3A, and dronedarone can interact with drugs that are substrates of CYP 3A and CYP 2D6.

Dronedarone has no significant potential to inhibit CYP 1A2, CYP 2C9, CYP 2C19, CYP 2C8 and CYP 2B6. It has the potential to inhibit P-glycoprotein (P-gP) transport.

Pharmacodynamic interactions can be expected with beta-blockers; calcium antagonists and digoxin [see Drug Interactions ].

In clinical trials, patients treated with dronedarone received concomitant medications including beta-blockers, digoxin, calcium antagonists (including those with heart rate-lowering effects), statins and oral anticoagulants.

[see Contraindications (4) ].

[see Drug Interaction ] and possible pharmacodynamic interaction, reconsider the need for digoxin therapy. If digoxin treatment is continued, halve the dose of digoxin, monitor serum levels closely, and observe for toxicity.

[see Drug Interactions ].

[see Drug Interactions ].

[see Contraindications (4) ].

[see Drug Interactions (7.1, 7.3) ].

[see Drug Interactions ].

[see Drug Interaction ]. Other CYP 2D6 substrates, including other beta-blockers, tricyclic antidepressants, and selective serotonin reuptake inhibitors (SSRIs) may have increased exposure upon co-administration with dronedarone.

[see Drug Interactions ]. Other P-gP substrates are expected to have increased exposure when coadministered with dronedarone.

Warfarin and losartan (CYP 2C9 substrates)

In healthy subjects, dronedarone at a dose of 600 mg twice daily increased S-warfarin exposure by 1.2-fold with no change in R-warfarin and with no clinically significant increase in INR. In clinical trials in patients with AF/AFL, there was no observed excess risk of bleeding compared to placebo when dronedarone was co-administered with oral anticoagulants. Monitor INR per the warfarin label.

No interaction was observed between dronedarone and losartan.

Theophylline (CYP 1A2 substrate)

Dronedarone does not increase steady state theophylline exposure.

Oral contraceptives

No decreases in ethinylestradiol and levonorgestrel concentrations were observed in healthy subjects receiving dronedarone concomitantly with oral contraceptives.

OVERDOSAGE

In the event of overdosage, monitor the patient's cardiac rhythm and blood pressure. Treatment should be supportive and based on symptoms.

It is not known whether dronedarone or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis or hemofiltration).

There is no specific antidote available.

CONTRAINDICATIONS

MULTAQ is contraindicated in patients with:

• NYHA Class IV heart failure or NYHA Class II — III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic [see Boxed Warning and Clinical Studies ]
• Second- or third-degree atrioventricular (AV) block or sick sinus syndrome (except when used in conjunction with a functioning pacemaker)
• Bradycardia less than 50 bpm
• Concomitant use of strong CYP 3A inhibitors, such as ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, and ritonavir [see Drug Interactions ]
• Concomitant use of drugs or herbal products that prolong the QT interval and might increase the risk of Torsade de Pointes, such as phenothiazine anti-psychotics, tricyclic antidepressants, certain oral macrolide antibiotics, and Class I and III antiarrhythmics
• QTc Bazett interval greater than or equal to 500 ms or PR interval >280 ms
• Severe hepatic impairment
• Pregnancy (Category X): MULTAQ may cause fetal harm when administered to a pregnant woman. MULTAQ is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations ].
• Nursing mothers [see Use in Specific Populations ]