Ciprofloxacine PCH may be available in the countries listed below.
Ciprofloxacin hydrochloride (a derivative of Ciprofloxacin) is reported as an ingredient of Ciprofloxacine PCH in the following countries:
International Drug Name Search
Temporarily relieving cough due to the common cold, hay fever, upper respiratory tract infections, sinus inflammation, sore throat, or bronchitis.
Dextromethorphan Polistirex Extended-Release Liquid is a cough suppressant. It works in the cough center of the brain to reduce a dry or nonproductive cough.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Dextromethorphan Polistirex Extended-Release Liquid. Tell your health care provider if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Dextromethorphan Polistirex Extended-Release Liquid. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Dextromethorphan Polistirex Extended-Release Liquid may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Dextromethorphan Polistirex Extended-Release Liquid as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Dextromethorphan Polistirex Extended-Release Liquid.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Dizziness; drowsiness; stomach upset.
Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue).
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Dextromethorphan Polistirex side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include confusion; excitement; hallucinations; slowed breathing.
Store Dextromethorphan Polistirex Extended-Release Liquid between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Dextromethorphan Polistirex Extended-Release Liquid out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Dextromethorphan Polistirex Extended-Release Liquid. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Unicordium may be available in the countries listed below.
Bepridil hydrochloride (a derivative of Bepridil) is reported as an ingredient of Unicordium in the following countries:
International Drug Name Search
Generic Name: acetaminophen, dexbrompheniramine, and pseudoephedrine (a SEET a MIN oh fen, dex brom fen EER a meen, and soo doe e FED rin)
Brand Names: Drixoral Allergy Sinus, Drixoral Cold and Flu, Drixoral Sinus
Acetaminophen is a pain reliever and fever reducer.
Dexbrompheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.
Pseudoephedrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).
The combination of acetaminophen, dexbrompheniramine, and pseudoephedrine is used to treat headache, fever, body aches, runny or stuffy nose, sneezing, itching, watery eyes, and sinus congestion caused by allergies, the common cold, or the flu.
Acetaminophen, dexbrompheniramine, and pseudoephedrine may also be used for purposes not listed in this medication guide.
Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:
liver disease, cirrhosis, or a history of alcoholism;
a blockage in your digestive tract (stomach or intestines);
diabetes;
kidney disease;
epilepsy or other seizure disorder;
cough with mucus, or cough caused by smoking, emphysema, or chronic bronchitis;
enlarged prostate or urination problems;
low blood pressure;
pheochromocytoma (an adrenal gland tumor); or
if you take potassium (Cytra, Epiklor, K-Lyte, K-Phos, Kaon, Klor-Con, Polycitra, Urocit-K).
Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. This medicine is usually taken only for a short time until your symptoms clear up.
Do not take for longer than 7 days in a row. Stop taking the medicine and call your doctor if you still have a fever after 3 days of use, you still have pain after 7 days (or 5 days if treating a child), if your symptoms get worse, or if you have a skin rash, ongoing headache, or any redness or swelling.
Since this medicine is taken when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.
Overdose symptoms may also include severe forms of some of the side effects listed in this medication guide.
chest pain, rapid pulse, fast or uneven heart rate;
confusion, hallucinations, severe nervousness;
tremor, seizure (convulsions);
easy bruising or bleeding, unusual weakness;
urinating less than usual or not at all;
nausea, pain in your upper stomach, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of your skin or eyes); or
dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, chest pain, shortness of breath, uneven heartbeats, seizure).
Less serious side effects may include:
dizziness, drowsiness;
mild headache;
dry mouth, nose, or throat;
constipation;
blurred vision;
feeling nervous; or
sleep problems (insomnia);
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Tell your doctor about all other medicines you use, especially:
leflunomide (Arava);
topiramate (Topamax);
zonisamide (Zonegran);
an antibiotic, antifungal medicine, sulfa drug, or tuberculosis medicine;
an antidepressant;
birth control pills or hormone replacement therapy;
bladder or urinary medications;
blood pressure medication;
a bronchodilator;
cancer medicine;
cholesterol-lowering medications such as Lipitor, Niaspan, Zocor, Vytorin, and others;
gout or arthritis medications (including gold injections);
HIV/AIDS medication;
medication for nausea and vomiting, stomach ulcers, or irritable bowel syndrome;
medicines to treat psychiatric disorders;
an NSAID such as Advil, Aleve, Arthrotec, Cataflam, Celebrex, Indocin, Motrin, Naprosyn, Treximet, Voltaren, others; or
seizure medication.
This list is not complete and other drugs may interact with acetaminophen, dexbrompheniramine, and pseudoephedrine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.
Antra MUPS may be available in the countries listed below.
Omeprazole magnesium salt (a derivative of Omeprazole) is reported as an ingredient of Antra MUPS in the following countries:
International Drug Name Search
Antac may be available in the countries listed below.
Ranitidine hydrochloride (a derivative of Ranitidine) is reported as an ingredient of Antac in the following countries:
International Drug Name Search
Mevir may be available in the countries listed below.
Brivudine is reported as an ingredient of Mevir in the following countries:
International Drug Name Search
Relieving symptoms of sinus congestion, runny nose, sneezing, itchy nose or throat, itchy or watery eyes, and cough due to colds, upper respiratory infections, and allergies. It may also be used for other conditions as determined by your doctor.
Dicel DM Chewables Chewable Tablets are a decongestant, antihistamine, and cough suppressant combination. The decongestant works by constricting blood vessels and reducing swelling in the nasal passages. The antihistamine works by blocking the action of histamine, which helps reduce symptoms such as watery eyes and sneezing. The cough suppressant works in the brain to help decrease the cough reflex to reduce a dry cough.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Dicel DM Chewables Chewable Tablets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Dicel DM Chewables Chewable Tablets. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Dicel DM Chewables Chewable Tablets may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Dicel DM Chewables Chewable Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Dicel DM Chewables Chewable Tablets.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Constipation; diarrhea; dizziness; drowsiness; dry mouth, nose, or throat; excitability; headache; loss of appetite; nausea; nervousness or anxiety; trouble sleeping; upset stomach; vomiting; weakness.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); difficulty urinating or inability to urinate; fast or irregular heartbeat; fever, chills, or persistent sore throat; hallucinations; loss of coordination; mental or mood changes (eg, depression); seizures; severe dizziness, drowsiness, light-headedness, or headache; severe dryness of the mouth, nose, and throat; severe or persistent trouble sleeping; shortness of breath; tremor; unusual bruising or bleeding; unusual tiredness or weakness; vision changes (eg, double vision, severe or persistent blurred vision).
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Dicel DM Chewables side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include blurred vision; confusion; flushing; hallucinations; mental or mood changes; muscle spasms; seizures; severe dizziness, light-headedness, or headache; severe drowsiness; trouble breathing; unusually fast, slow, or irregular heartbeat; vomiting.
Store Dicel DM Chewables Chewable Tablets at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Dicel DM Chewables Chewable Tablets out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Dicel DM Chewables Chewable Tablets. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Naproxen-E may be available in the countries listed below.
Naproxen is reported as an ingredient of Naproxen-E in the following countries:
International Drug Name Search
Tevox may be available in the countries listed below.
Levofloxacin is reported as an ingredient of Tevox in the following countries:
International Drug Name Search
Cigarette smoking increases the risk of serious heart problems associated with use of Drospirenone/Ethinyl Estradiol. This risk increases with age and with heavy smoking (15 or more cigarettes per day). Women who are older than 35 years old have a greater risk. Women who use Drospirenone/Ethinyl Estradiol should not smoke.
Preventing pregnancy. It may also be used for other conditions as determined by your doctor.
Drospirenone/Ethinyl Estradiol is a progesterone and estrogen combination birth control pill. It works by preventing ovulation, thickening the mucus in the cervix, and changing the lining of the uterus.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Drospirenone/Ethinyl Estradiol. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Drospirenone/Ethinyl Estradiol. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Drospirenone/Ethinyl Estradiol may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Drospirenone/Ethinyl Estradiol as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Drospirenone/Ethinyl Estradiol.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Breast tenderness; bleeding or spotting between menstrual periods; nausea; stomach cramps or bloating; vomiting; weight gain.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); breast lump or discharge; calf or leg pain, swelling, or tenderness; change in the amount of urine produced; chest pain or heaviness; confusion; coughing of blood; fainting; irregular heartbeat; left-sided jaw, neck, shoulder, or arm pain; mental or mood changes (eg, depression); migraines; missed menstrual period; numbness of an arm or leg; one-sided weakness; persistent, severe, or recurring headache or dizziness; persistent vaginal spotting; severe or persistent trouble sleeping; severe stomach pain or tenderness; shortness of breath; slurred speech; sudden severe vomiting; swelling of the fingers, hands, legs, or ankles; symptoms of liver problems (eg, yellowing of the skin or eyes, fever, dark urine, pale stools, loss of appetite); unusual or severe vaginal bleeding; unusual tiredness or weakness; vaginal irritation or discharge; vision changes (eg, sudden vision loss, double vision).
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Drospirenone/Ethinyl Estradiol side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include severe nausea; unexplained vaginal bleeding.
Store Drospirenone/Ethinyl Estradiol at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Drospirenone/Ethinyl Estradiol out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Drospirenone/Ethinyl Estradiol. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Waxol may be available in the countries listed below.
Docusate Sodium is reported as an ingredient of Waxol in the following countries:
International Drug Name Search
Class: Class III Antiarrhythmics
VA Class: CV300
Chemical Name: N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]-methanesulfonamide monohydrochloride
Molecular Formula: C31H44N2O5S•HCl
CAS Number: 141625-93-6
Brands: Multaq
Special Alerts:
[Posted 07/21/2011] ISSUE: FDA notified healthcare professionals that it is reviewing data from a clinical trial that evaluated the effects of the antiarrhythmic drug dronedarone (Multaq) in patients with permanent atrial fibrillation. The study was stopped early after the data monitoring committee found a two-fold increase in death, as well as two-fold increases in stroke and hospitalization for heart failure in patients receiving dronedarone compared to patients taking a placebo. FDA is evaluating whether and how the preliminary results of the PALLAS study apply to patients taking dronedarone for paroxysmal or persistent atrial fibrillation or atrial flutter. The PALLAS study results are considered preliminary at this time because the data have not undergone quality assurance procedures and have not been completely adjudicated. FDA will update the public when more information is available.
BACKGROUND: Dronedarone is approved for use to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted.
RECOMMENDATION: At this time, patients taking dronedarone should talk to their healthcare professional about whether they should continue to take dronedarone for non-permanent atrial fibrillation. Patients should not stop taking dronedarone without talking to a healthcare professional. Healthcare professionals should not prescribe dronedarone to patients with permanent atrial fibrillation. See the Data Summary in the Drug Safety Communication for additional details at: . For more information visit the FDA website at: and .
REMS:
FDA approved a REMS for dronedarone hydrochloride to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of dronedarone hydrochloride and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().
Contraindicated in patients with NYHA class IV heart failure or NYHA class II or III heart failure with recent decompensation requiring hospitalization or referral to a specialized heart failure clinic.1 (See Heart Failure under Cautions.)
In the ANDROMEDA study in patients with severe heart failure requiring recent hospitalization or referral to a specialized heart failure clinic for worsening symptoms, dronedarone therapy was associated with a greater than twofold increase in mortality rate relative to placebo;1 4 do not use dronedarone in such patients.1
Class III antiarrhythmic agent;5 6 7 also appears to exhibit activity in each of the 4 Vaughan-Williams antiarrhythmic classes.1 5 6 8
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Reduction of risk of hospitalization for cardiovascular events in patients with paroxysmal or persistent atrial fibrillation or atrial flutter who have had a recent episode of atrial fibrillation/flutter and who have associated cardiovascular risk factors (i.e., >70 years of age, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≥50 mm, or left ventricular ejection fraction <40%); used in such patients who are in sinus rhythm or who will undergo cardioversion.1 9 (See Boxed Warningand also see Contraindications and see Heart Failure under Cautions.)
Less effective than amiodarone in preventing recurrence of atrial fibrillation but appears to have an improved safety profile (based on short-term data).4 5 8 9 14 16 19 24 Long-term data and experience needed to elucidate relative safety and tolerability of dronedarone versus amiodarone because of some late-onset adverse effects of amiodarone (e.g., pulmonary toxicity).6 8 14 16 18 19
Efficacy of retreatment with dronedarone in patients who relapse after initial successful treatment or in those who fail therapy with amiodarone not established.17 21
Individualize treatment of atrial fibrillation/flutter based on relative benefits and risks of various therapies (e.g., rhythm versus rate control, nondrug therapies such as ablation and pacemaker implantation), patient age, and patient preference and tolerance of the arrhythmia.15 17 18 20 21 22 23 24 26
FDA-required Risk Evaluation and Mitigation Strategy (REMS) implemented to assist healthcare professionals with identification of appropriate patients to receive dronedarone and ensure safe use while minimizing risk.10 11 12
Goals of program (mPACT: MULTAQ Partnership for Appropriate Care and Treatment) are to educate prescribers about the increased risk of mortality associated with use of dronedarone in patients with NYHA class IV heart failure and in those who have NYHA class II or III heart failure with recent decompensation requiring hospitalization or referral to a specialized heart failure clinic, and to prevent use of the drug in such patients.12 Also designed to inform patients about serious risks associated with dronedarone, including an increased rate of mortality in patients with severe, unstable heart failure.12 (See Contraindicationsand also see Heart Failure under Cautions.) REMS program consists of educational materials for healthcare professionals and patients, including a medication guide to be dispensed with every dronedarone prescription.1 10 11 12
For additional information, consult the Multaq website at .10
Administer orally twice daily with morning and evening meals (to enhance bioavailability).1 (See Food under Pharmacokinetics.)
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Available as dronedarone hydrochloride; dosage expressed in terms of dronedarone.1
Reduction of risk of hospitalization due to cardiovascular events in selected patients with paroxysmal or persistent atrial fibrillation/flutter: 400 mg twice daily with morning and evening meals.1
Must discontinue class I or III antiarrhythmic agents and drugs that are potent inhibitors of cytochrome P450 (CYP) isoenzyme 3A prior to initiating dronedarone.1 9 (See Contraindications under Cautions and also see Interactions.)
The manufacturer states that no dosage other than 400 mg twice daily of dronedarone is recommended for any population at this time.9
No dosage adjustment required in patients with moderate hepatic impairment.1 Contraindicated in patients with severe hepatic impairment.1 (See Hepatic Impairment under Cautions.)
No dosage adjustment required.1 (See Renal Impairment under Cautions.)
NYHA Class IV heart failure or NYHA Class II or III heart failure with recent decompensation requiring hospitalization or referral to a specialized heart failure clinic.1 (See Boxed Warning and also see Heart Failure under Cautions.)
Second- or third-degree AV block or sick sinus syndrome (except in patients with a functioning pacemaker).1
Bradycardia (<50 beats/minute).1
QT interval corrected for rate, Bazett’s formula (QTc) of ≥500 msec or PR interval >280 msec.1 9 (See Prolongation of QT Interval under Cautions.)
Concomitant use of potent inhibitors of CYP3A (e.g., clarithromycin, cyclosporine, itraconazole, ketoconazole, nefazodone, ritonavir, telithromycin, voriconazole).1 (See Drugs Affecting Hepatic Microsomal Enzymes and also see Drugs Metabolized by Hepatic Microsomal Enzymes under Interactions.)
Concomitant use with drugs or herbal supplements that prolong the QT interval and may increase the risk of torsades de pointes (e.g., class I or III antiarrhythmic agents, phenothiazines, tricyclic antidepressants, certain oral macrolides).1 9 (See Drugs that Prolong the QT Interval under Interactions.)
Severe hepatic impairment.1 (See Hepatic Impairment and also see Severe Hepatic Injury under Cautions.)
Women who are or may become pregnant.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Nursing women.1
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
In ANDROMEDA study, greater than twofold increase relative to placebo in rate of mortality in dronedarone-treated patients with severe heart failure requiring recent hospitalization or referral to a specialized heart failure clinic for worsening symptoms; do not use dronedarone in such patients.1 4
Limited clinical experience available in patients with atrial fibrillation/flutter who develop worsening heart failure during therapy with dronedarone.1 Worsening heart failure complicated by multiorgan dysfunction (e.g., acute renal and hepatic failure) in the setting of dronedarone initiation reported during postmarketing surveillance in at least one patient with atrial fibrillation and history of NYHA class III-IV heart failure and multiple recent hospitalizations for heart failure.26
If heart failure develops or worsens, consider interrupting or discontinuing therapy.1
Contraindicated in patients with NYHA class IV heart failure or NYHA class II or III heart failure with recent decompensation requiring hospitalization or referral to a specialized heart failure clinic.1 (See Boxed Warningand also see Contraindications under Cautions.)
Severe hepatic injury reported rarely with dronedarone therapy.28 Acute hepatic failure requiring liver transplantation reported in at least 2 patients; in both cases, explanted liver showed evidence of extensive hepatocellular necrosis.28
Consider periodic monitoring of serum hepatic enzymes, especially during first 6 months of therapy.28 If hepatic injury suspected (e.g., anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, itching), discontinue dronedarone therapy promptly and assess serum hepatic enzymes and bilirubin; initiate appropriate therapy if hepatic injury found.28 Do not reinitiate dronedarone therapy in patients who experience hepatic injury without another explanation for such injury.28
Possible hypokalemia and hypomagnesemia with concomitant use of potassium-depleting diuretics.1 Ascertain that serum potassium and magnesium concentrations are within normal range prior to initiation of dronedarone; maintain within normal range during therapy.1 9 24
Moderate prolongation of QTc interval reported; QTc interval increased by an average of about 10 msec, however, greater prolongation reported.1 Discontinue dronedarone if QTc interval is ≥500 msec.1 (See Contraindications under Cautions.)
Increase in Scr of about 0.1 mg/dL reported following initiation of drug; however, may not necessarily indicate decline in renal function.1 2 4 5 13 16 Increase in Scr and decrease in Clcr by about 10–15 or 18%, respectively, observed in clinical studies in healthy individuals and patients receiving the drug; however, no clinically important change in glomerular filtration rate, renal plasma flow or electrolyte exchanges, or any structural renal damage reported.1 2 3 4 13 Change in Scr may result from a specific partial inhibition of tubular organic cation transporters and inhibition of tubular secretion of creatinine by dronedarone.1 5 13 16
Increases in Scr appear to have a rapid onset, reach a plateau after 7 days, and are reversible following discontinuance of the drug.1 13 If an increase in the Scr occurs and plateaus, use this increased value as the patient’s new baseline Scr.1
May cause fetal harm; teratogenicity demonstrated in animals.1
Avoid pregnancy during therapy; women of childbearing potential (i.e., premenopausal women who have not undergone hysterectomy or oophorectomy) must use effective contraception.1 If used during pregnancy or if patient becomes pregnant, apprise patient of potential fetal hazard.1 (See Advice to Patients.)
Contraindicated in women who are or may become pregnant.1
Category X.1 (See Fetal/Neonatal Morbidity and Mortality and also see Contraindications under Cautions.)
Dronedarone and its metabolites distributed into milk in rats; not known whether distributed into milk in humans.1 Discontinue nursing or the drug.1 Contraindicated in nursing women.1
Safety and efficacy not established in children or adolescents <18 years of age.1
No substantial differences in safety and efficacy relative to those in younger adults.1 (See Special Populations under Pharmacokinetics.)
Not studied in patients with severe hepatic impairment; limited clinical experience available in patients with moderate hepatic impairment.1 Severe liver injury reported rarely with dronedarone therapy.28 (See Severe Hepatic Injury under Cautions.) Contraindicated in patients with severe hepatic impairment.1 (See Special Populations under Pharmacokinetics.)
No dosage adjustment required because dronedarone undergoes minimal renal excretion.1 (See Special Populations and also see Elimination Route under Pharmacokinetics.)
Increased Scr (increase of ≥10% five days after initiation of drug),1 prolonged QTc interval (>450 msec [males] or >470 msec [females]),1 diarrhea,1 2 14 asthenia,1 nausea,1 2 skin reactions (e.g., rash [generalized, macular, maculo-papular, erythematous], pruritus, eczema, dermatitis, allergic dermatitis),1 2 abdominal pain,1 bradycardia,1 2 vomiting,1 dyspepsia.1 (See Contraindications and see Prolongation of QT Interval and also see Increased Serum Creatinine Concentrations under Cautions.)
Metabolized mainly by CYP isoenzyme 3A.1
Moderate inhibitor of CYP isoenzymes 3A and 2D6; does not appear to substantially inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2C8, or 2B6.1 May inhibit P-glycoprotein transport system.1
Potent inhibitors of CYP3A: Pharmacokinetic interaction (increased exposure to and peak plasma concentrations of dronedarone).1 Concomitant use contraindicated.1
Inhibitors of CYP3A: Potential pharmacokinetic interaction (altered concentrations of dronedarone).1
Inducers of CYP3A: Potential pharmacokinetic interaction (substantially decreased exposure to dronedarone).1 Avoid concomitant use.1
Substrates of CYP3A: Potential pharmacokinetic interaction (possible increased plasma concentrations of the CYP3A substrate).1 9 25 Monitor plasma concentrations and appropriately adjust dosage of CYP3A substrates with a narrow therapeutic index when administered orally.1 9 Some clinicians state that dronedarone should be used with caution in patients receiving drugs with a narrow therapeutic index that are metabolized by CYP3A4.25
Substrates of CYP2D6: Potential pharmacokinetic interaction (possible increased exposure to the CYP2D6 substrate).1
Pharmacologic interaction (potential risk of torsades de pointes-type ventricular tachycardia) with drugs or herbal supplements that prolong the QT interval; concomitant use contraindicated.1 9 (See Contraindications under Cautions.)
Potential pharmacokinetic interaction (increased exposure to substrates of P-glycoprotein transport system [e.g., digoxin] expected) when used concomitantly with dronedarone.1 Some clinicians state that dronedarone should be used with caution in patients receiving drugs with a narrow therapeutic index that are metabolized by the P-glycoprotein transport system.25
Drug | Interaction | Comments |
|---|---|---|
Antiarrhythmic agents, class I or III (e.g., amiodarone, disopyramide, dofetilide, flecainide, propafenone, quinidine, sotalol) | Potential risk of torsades de pointes-type ventricular tachycardia1 | Concomitant use contraindicated1 |
Anticoagulants, oral (e.g., warfarin) | Increased exposure to S-warfarin in healthy individuals; no change in exposure to R-warfarin or clinically important increases in the INR1 No excess risk of bleeding observed with concomitant use of dronedarone and oral anticoagulants in patients with atrial fibrillation/flutter1 | Monitor INR according to manufacturers’ labeling for warfarin1 |
Antidepressants, SSRI | Possible increased exposure to SSRI1 | |
Antidepressants, tricyclic | Potential risk of torsades de pointes-type ventricular tachycardia1 Possible increased exposure to tricyclic antidepressants1 | Concomitant use contraindicated1 |
β-Adrenergic blocking agents (e.g., metoprolol, propranolol) | Increased incidence of bradycardia observed1 Increased exposure to metoprolol and propranolol; possible increased exposure to other β-adrenergic blocking agents that are CYP2D6 substrates1 | If used with β-adrenergic blocking agents, use lower initial dosage of the β-adrenergic blocking agent and increase dosage of β-adrenergic blocker only if well tolerated as documented by ECG1 9 |
Calcium-channel blocking agents (e.g., diltiazem, nifedipine, verapamil) | Calcium-channel blocking agents with depressant effects on the sinus and AV nodes may potentiate the conduction effects of dronedarone1 Dronedarone increases exposure to calcium-channel blocking agents (verapamil, diltiazem, nifedipine); verapamil and diltiazem increase exposure to dronedarone1 | If used with calcium-channel blocking agents, use lower initial dosage of the calcium-channel blocking agent and increase dosage of calcium-channel blocker only if well tolerated as documented by ECG1 9 |
Carbamazepine | Substantially decreased exposure to dronedarone due to CYP3A induction1 | Avoid concomitant use1 |
Cyclosporine | Increased peak plasma concentrations of, and exposure to, dronedarone1 | Concomitant use contraindicated1 |
Digoxin | Possible potentiation of electrophysiologic effects of dronedarone (e.g., decreased AV node conduction)1 Increased exposure to digoxin and increased digoxin concentrations1 Increased incidence of GI disorders observed1 | When initiating dronedarone therapy, reassess need for continued digoxin therapy; discontinue digoxin or reduce digoxin dosage by 50%1 Monitor serum digoxin concentrations; close observation for signs of digoxin toxicity recommended1 |
Grapefruit juice | Increased peak plasma concentrations of, and exposure to, dronedarone1 | Avoid grapefruit juice during dronedarone therapy1 9 |
HMG-CoA reductase inhibitors (statins) | Increased exposure to simvastatin and simvastatin acid1 | Consult manufacturer’s labeling for the respective statin for specific recommendations regarding concomitant use with CYP3A or P-glycoprotein transport system inhibitors such as dronedarone1 |
Itraconazole | Increased peak plasma concentrations of, and exposure to, dronedarone1 | Concomitant use contraindicated1 |
Ketoconazole | Increased peak plasma concentrations of, and exposure to, dronedarone1 | Concomitant use contraindicated1 |
Losartan | No drug interaction observed1 | |
Macrolides | Clarithromycin, telithromycin: Increase exposure to and peak plasma concentrations of dronedarone1 Certain oral macrolides: Potential risk of torsades de pointes-type ventricular tachycardia1 | Clarithromycin, telithromycin, and certain oral macrolides: Concomitant use with dronedarone contraindicated1 |
Nefazodone | Increased peak plasma concentrations of, and exposure to, dronedarone1 | Concomitant use contraindicated1 |
Oral contraceptives | No decreases in ethinyl estradiol or levonorgestrel concentrations observed in healthy individuals1 | |
Pantoprazole | No clinically important effect on the pharmacokinetics of dronedarone1 | |
Phenobarbital | Substantially decreased exposure to dronedarone due to CYP3A induction1 | Avoid concomitant use1 |
Phenothiazines | Potential risk of torsades de pointes-type ventricular tachycardia1 | Concomitant use contraindicated1 |
Phenytoin | Substantially decreased exposure to dronedarone due to CYP3A induction1 | Avoid concomitant use1 |
Potassium-depleting diuretics | Possible hypokalemia or hypomagnesemia1 | Ascertain that serum potassium and magnesium concentrations are within normal range prior to initiation of dronedarone; maintain within normal range during therapy1 |
Rifampin | Decreased exposure to dronedarone due to CYP3A induction1 | Avoid concomitant use1 |
Ritonavir | Increased peak plasma concentrations of, and exposure to, dronedarone1 | Concomitant use contraindicated1 |
St. John’s wort | Substantially decreased exposure to dronedarone due to CYP3A induction1 | Avoid concomitant use1 |
Sirolimus | Possible increased plasma concentrations of sirolimus;1 initiation of dronedarone therapy in one patient receiving sirolimus post-kidney transplantation resulted in a threefold increase in trough sirolimus concentrations from baseline25 | Monitor plasma concentrations of sirolimus and adjust dosage appropriately when used concomitantly with dronedarone1 Some clinicians recommend avoidance of concurrent use of sirolimus and dronedarone when possible. If concurrent administration cannot be avoided, a 50–75% reduction in sirolimus dosage prior to dronedarone initiation has been suggested; monitor trough sirolimus concentrations regularly (possibly even daily) during titration phase25 |
Tacrolimus | Possible increased plasma concentrations of tacrolimus1 | Monitor plasma concentrations of tacrolimus and adjust dosage appropriately during concomitant use1 |
Theophylline | No apparent increase in steady-state exposure to theophylline1 | |
Voriconazole | Increased peak plasma concentrations of, and exposure to, dronedarone1 | Concomitant use contraindicated1 |
Low systemic bioavailability; undergoes first-pass metabolism.1 Absolute bioavailability about 4% when administered without food.1
Steady-state concentrations achieved within 4–8 days following repeated oral administration of dronedarone 400 mg twice daily.1
Food increases bioavailability; bioavailability approximately 15% when administered with a high-fat meal.1
Peak plasma concentrations of dronedarone and N-debutyl metabolite reached within 3–6 hours following oral administration with food.1
Exposure to dronedarone increased by 23% in patients ≥65 years of age compared with that in younger adults.1 (See Geriatric Use under Cautions.)
Mean exposure to dronedarone increased by 1.3-fold in patients with moderate hepatic impairment compared with individuals with normal hepatic function; mean exposure to N-debutyl metabolite decreased by about 50%.1 (See Hepatic Impairment under Cautions.)
Pharmacokinetics not studied in patients with severe hepatic impairment; contraindicated in such patients.1
No apparent differences in pharmacokinetics observed in healthy individuals with mild or moderate renal impairment versus those with normal renal function, or in patients with atrial fibrillation and mild to severe renal impairment versus those with normal renal function.1 9 (See Renal Impairment under Cautions.)
Exposure to dronedarone averages 30% higher in women than in men.1
Pharmacokinetic differences related to race not formally studied.1 However, based on a cross-study comparison, exposure to dronedarone twofold higher in Asian men (of Japanese ancestry) than in Caucasian men following single-dose administration of dronedarone 400 mg.1
Dronedarone and its metabolites distributed into milk in rats; not known whether distributed into human milk.1
Dronedarone and N-debutyl metabolite are >98% bound to plasma proteins (mainly albumin); binding not saturable.1
Extensively metabolized, mainly by CYP3A.1
Initial metabolic pathway includes N-debutylation to form active N-debutyl metabolite, oxidative deamination to form inactive propanoic acid metabolite, and direct oxidation.1 Metabolites further metabolized to >30 uncharacterized metabolites.1 N-debutyl metabolite exhibits pharmacodynamic activity; only up to one-third as potent as dronedarone.1
Excreted in urine (6%) and in feces (84%) mainly as metabolites; no unchanged drug excreted in urine.1
13–19 hours following IV administration.1
25°C (may be exposed to 15–30°C).1
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Mechanism of antiarrhythmic action not fully elucidated; exact contribution of activities in each of the 4 Vaughan-Williams antiarrhythmic classes to the clinical effect of the drug unknown.1 5
Benzofuran derivative structurally related to amiodarone, but with structural modifications that include removal of the iodine group and addition of a methane-sulfonyl group.1 2 3 5 6 7 8 16
Removal of the iodine group intended to reduce risk of nontarget organ (e.g., thyroid, pulmonary) adverse effects associated with amiodarone therapy; addition of the methane-sulfonyl group aimed at reducing lipophilicity, decreasing risk of neurotoxic adverse effects, and shortening half-life of dronedarone.2 3 5 6 8 16
Electrophysiologic profile similar to amiodarone, but with different relative effects on individual ion channels.2 3 4 5 6
Prolongs action potential duration (APD) mainly by inhibition of potassium channels, including transmembrane delayed rectifier, ultrarapid delayed rectifier, inward rectifier, and transient outward potassium currents.5 6
Inhibits sodium currents (at rapid pacing rates), calcium channels and slow L-type calcium currents, and demonstrates noncompetitive, antiadrenergic (α- and β-blocking) activity.5 6 8 16
Prolongs PR interval and slows sinus rate by prolonging atrial and ventricular refractory periods.1 8
Prolongs RR and QT intervals.5 6
Produces a dose-dependent increase in PR interval and a moderate prolongation of the QTc interval similar to amiodarone.1 5 8
Importance of instructing patients to carefully read the manufacturer’s patient information (medication guide) before initiating therapy and each time the prescription is refilled.1
Importance of informing clinician if signs or symptoms of heart failure (e.g., weight gain, dependent edema, increasing shortness of breath) occur.1
Importance of advising patients receiving dronedarone to immediately report symptoms suggesting hepatic injury (e.g., anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, itching).28
Importance of taking dronedarone with a meal.1
Importance of advising patients to avoid grapefruit juice while taking dronedarone.1 (See Specific Drugs and Food under Interactions.)
Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed; necessity of advising women to avoid pregnancy and breast-feeding during dronedarone therapy.1 9 Necessity of advising women of childbearing potential to use an effective method of contraception while receiving therapy and importance of advising these patients regarding appropriate contraceptive choices (taking into consideration their underlying medical conditions and lifestyle preferences).1 If pregnancy occurs, advise patient of risk to the fetus.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements (e.g., St. John’s wort), as well as any concomitant illnesses (e.g., heart failure, rhythm disturbance other than atrial fibrillation/flutter, uncorrected hypokalemia).1
Importance of advising patients that if a dose of dronedarone is missed, the next dose should be taken at the regularly scheduled time; the dose should not be doubled.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 400 mg (of dronedarone) | Multaq | Sanofi-Aventis |
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Multaq 400MG Tablets (SANOFI-AVENTIS U.S.): 60/$276.00 or 180/$766.01
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Sanofi-Aventis. Multaq (dronedarone hydrochloride) tablets prescribing information. Bridgewater, NJ; 2009 Jul.
2. Hohnloser SH, Crijns HJ, van Eickels M et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009; 360:668-78. [PubMed 19213680]
3. Singh BN, Connolly SJ, Crijns HJ et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007; 357:987-99. [PubMed 17804843]
4. Køber L, Torp-Pedersen C, McMurray JJ et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008; 358:2678-87. [PubMed 18565860]
5. Hoy SM, Keam SJ. Dronedarone. Drugs. 2009; 69:1647-63. [PubMed 19678715]
6. Riera AR, Uchida AH, Ferreira C et al. Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome. Cardiol J. 2008; 15:209-19. [PubMed 18651412]
7. Coletta AP, Cleland JG, Cullington D et al. Clinical trials update from Heart Rhythm 2008 and Heart Failure 2008: ATHENA, URGENT, INH study, HEART and CK-1827452. Eur J Heart Fail. 2008; 10:917-20. [PubMed 18678526]
8. Garcia D, Cheng-Lai A. Dronedarone: a new antiarrhythmic agent for the treatment of atrial fibrillation. Cardiol Rev. 2009 Sep-Oct; 17:230-4.
9. Sanofi-Aventis, Bridgewater, NJ: Personal communication.
10. Sanofi-Aventis. Healthcare professional information sheet for Multaq (dronedarone). 2009 Jul. Available from website. Accessed 2010 Mar 11.
11. Sanofi-Aventis. Prescribing Multaq: Information for health care professionals. 2009 Dec. Available from website. Accessed 2010 Mar 18.
12. Sanofi-Aventis. Risk evaluation and mitigation strategy (REMS): NDA 22-425 Multaq (dronedarone). 2009 Jun 9. Available from website. Accessed 2010 Mar 18.
13. Tschuppert Y, Buclin T, Rothuizen LE et al. Effect of dronedarone on renal function in healthy subjects. Br J Clin Pharmacol. 2007; 64:785-91. [PubMed 17662087]
14. Le Heuzey JY, De Ferrari GM, Radzik D et al. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation. The DIONYSOS study. J Cardiovasc Electrophysiol. 2010 Jun; 21:597-605. [PubMed 20384650]
15. Savelieva I, Camm J. Update on atrial fibrillation: part II. Clin Cardiol. 2008; 31:102-8. [PubMed 18383050]
16. Zimetbaum PJ. Dronedarone for atrial fibrillation—an odyssey. N Engl J Med. 2009 Apr; 360:1811-3. Commentary. [PubMed 19403901]
17. Schafer JA, Kjesbo NK, Gleason PP. Dronedarone: current evidence and future questions. Cardiovasc Ther. 2010; 28:38-47. [PubMed 20074258]
18. Singh D, Cingolani E, Diamond GA et al. Dronedarone for atrial fibrillation. Have we expanded the therapeutic armamentarium? JACC. 2010; 55:1569-76. Commentary. [PubMed 20378073]
19. Ezekowitz MD. Maintaining sinus rhythm—making treatment better than the disease. N Engl J Med. 2009; 357:1039-41. Editorial. [PubMed 17804851]
20. Wyse DG, Waldo AL, DiMarco JP et al, for theAtrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002 Dec 5;347:1825-33. [PubMed 12466506]
21. Falk RH. Management of atrial fibrillation—radical reform or modest modification? N Engl J Med. 2002; 347:1883-4. Editorial. [PubMed 12466514]
22. Opolski G, Torbicki A, Kosior D
