Zanmbeel

Sunday, July 4, 2010

Amitriptyline and chlordiazepoxide

MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088622.pdf, must be dispensed with this medication for each new outpatient prescription and refill.

U.S. BRAND NAMES — Limbitrol®; Limbitrol® DS [DSC]

PHARMACOLOGIC CATEGORY
Antidepressant, Tricyclic (Tertiary Amine)
Benzodiazepine

DOSING: ADULTS — Depression and anxiety: Oral: Initial: 3-4 tablets in divided doses; this may be increased to 6 tablets/day as required. Some patients respond to smaller doses and can be maintained on 2 tablets.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet: 12.5/5: Amitriptyline hydrochloride 12.5 mg and chlordiazepoxide 5 mg; 25/10: Amitriptyline hydrochloride 25 mg and chlordiazepoxide 10 mg
Limbitrol®: 12.5/5: Amitriptyline hydrochloride 12.5 mg and chlordiazepoxide 5 mg
Limbitrol® DS: 25/10: Amitriptyline hydrochloride 25 mg and chlordiazepoxide 10 mg [DSC]

DOSAGE FORMS: CONCISE
Tablet: 12.5/5: Amitriptyline 12.5 mg and chlordiazepoxide 5 mg; 25/10: Amitriptyline 25 mg and chlordiazepoxide 10 mg
Limbitrol®: 12.5/5: Amitriptyline 12.5 mg and chlordiazepoxide 5 mg

GENERIC EQUIVALENT AVAILABLE — Yes

USE — Treatment of moderate-to-severe anxiety and/or agitation and depression

ADVERSE REACTIONS SIGNIFICANT — See individual agents.

CONTRAINDICATIONS — Hypersensitivity to benzodiazepines, tricyclic antidepressants, or any component of the formulation; depression of CNS; MAO inhibitors; acute recovery phase following MI; angle-closure glaucoma; pregnancy

WARNINGS / PRECAUTIONS
Boxed warnings: Suicidal thinking/behavior: See "Major psychiatric warnings" below.

Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥ 65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Amitriptyline and chlordiazepoxide combination is FDA approved for depression associated with anxiety in children ≥ 12 years of age. The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. This combination is not FDA approved for the treatment of bipolar depression.

Concerns related to adverse effects: Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia. Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by amitriptyline is very high relative to other antidepressants. Orthostatic hypotension: May cause orthostatic hypotension (risk is very high relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia). Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients. Sedation: Both agents may cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). The degree of sedation is very high relative to other antidepressants. SIADH and hyponatremia: Has been associated with the development of SIADH and hyponatremia.

Disease-related concerns: Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities); the risk conduction abnormalities with amitriptyline is high relative to other antidepressants. Depression: Use chlordiazepoxide with caution in patients with depression, particularly if suicidal risk may be present. Drug abuse: Use chlordiazepoxide with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Diabetes: Use amitriptyline with caution in patients with diabetes mellitus; may alter glucose regulation. Hepatic impairment: Use both agents with caution in patients with hepatic impairment. Impaired gag reflux: Use chlordiazepoxide with caution in patients with an impaired gag reflux. Porphyria: Use chlordiazepoxide with caution in patients with porphyria. Renal impairment: Use both agents with caution in patients with renal impairment. Respiratory disease: Use chlordiazepoxide with caution in patients with respiratory disease. Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Thyroid dysfunction: Use with caution in patients with hyperthyroidism or those receiving thyroid supplementation.

Concurrent drug therapy issues: CNS depressants/psychoactive medications: Use chlordiazepoxide with caution in patients receiving other CNS depressants or psychoactive medication. Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations: Debilitated patients: Use chlordiazepoxide with caution in debilitated patients; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects. Elderly: Use both agents with caution in the elderly. Benzodiazepines have been associated with falls and traumatic injury; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects. Pediatrics: Use chlordiazepoxide with caution in children; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects.

Dosage form specific issues: Chlordiazepoxide injection: Parenteral administration should be avoided in comatose patients or shock. Adequate resuscitative equipment/personnel should be available, and appropriate monitoring should be conducted at the time of injection and for several hours following administration. The parenteral formulation should be diluted for I.M. administration with the supplied diluent only. This diluent should not be used when preparing the drug for intravenous administration.

Other warnings/precautions: Appropriate use: Chlordiazepoxide does not have analgesic, antidepressant, or antipsychotic properties. Discontinuation of therapy: Amitriptyline therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods. Rebound or withdrawal symptoms may occur following abrupt discontinuation of chlordiazepoxide or large decreases in dose. Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy. Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.

RESTRICTIONS — C-IV

METABOLISM / TRANSPORT EFFECTS
Amitriptyline: Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak)

Chlordiazepoxide: Substrate of CYP3A4 (major)

DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Alpha-/Beta-Agonists (Direct-Acting): Tricyclic Antidepressants may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Exceptions: Dipivefrin. Risk D: Consider therapy modification

Alpha1-Agonists: Tricyclic Antidepressants may enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification

Alpha2-Agonists: Tricyclic Antidepressants may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification

Altretamine: May enhance the orthostatic effect of Tricyclic Antidepressants. Risk C: Monitor therapy

Amphetamines: Tricyclic Antidepressants may enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Risk C: Monitor therapy

Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification

Aprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy

Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Aspirin: Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification

Beta2-Agonists: Tricyclic Antidepressants may enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy

BuPROPion: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification

CarBAMazepine: May increase the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy

Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Cimetidine: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Cimetidine: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy

Cinacalcet: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Cisapride: Amitriptyline may enhance the arrhythmogenic effect of Cisapride. Risk X: Avoid combination

Clozapine: Benzodiazepines may enhance the adverse/toxic effect of Clozapine. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Desmopressin: Tricyclic Antidepressants may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy

Dexmethylphenidate: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Disulfiram: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy

Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination

DULoxetine: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Fluconazole: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification

Fosaprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Specifically, the active metabolite aprepitant is likely responsible for this effect. Risk C: Monitor therapy

Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification

Grapefruit Juice: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification

Iobenguane I 123: Tricyclic Antidepressants may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination

Isoniazid: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy

Lithium: May enhance the neurotoxic effect of Tricyclic Antidepressants. Risk C: Monitor therapy

Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Macrolide Antibiotics: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification

MAO Inhibitors: May enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. Risk X: Avoid combination

MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy

Methylphenidate: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Nefazodone: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification

Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

NSAID (COX-2 Inhibitor): Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). Risk C: Monitor therapy

NSAID (Nonselective): Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy

Oral Contraceptive (Estrogens): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy

Oral Contraceptive (Progestins): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

Phenytoin: Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Risk C: Monitor therapy

Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification

Propoxyphene: May enhance the CNS depressant effect of Tricyclic Antidepressants. Risk C: Monitor therapy

Protease Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Management: Amprenavir, atazanavir, darunavir, indinavir, nelfinavir, ritonavir, and tipranavir are contraindicated with midazolam and triazolam according to each protease inhibitor's prescribing information. Risk D: Consider therapy modification

Protease Inhibitors: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

Proton Pump Inhibitors: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Exceptions: Lansoprazole; Pantoprazole; Rabeprazole. Risk C: Monitor therapy

QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification

QuiNIDine: Tricyclic Antidepressants may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification

QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Rifamycin Derivatives: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Citalopram; Escitalopram; PARoxetine; Sertraline. Risk C: Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification

Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination

St Johns Wort: May increase the metabolism of Tricyclic Antidepressants. The risk of serotonin syndrome may theoretically be increased. Risk D: Consider therapy modification

St Johns Wort: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy

Sulfonylureas: Cyclic Antidepressants may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Terbinafine: May decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification

Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination

Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification

Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

TraMADol: Tricyclic Antidepressants may enhance the neuroexcitatory and/or seizure-potentiating effect of TraMADol. Risk C: Monitor therapy

Valproic Acid: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Tricyclic Antidepressants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Yohimbine: Tricyclic Antidepressants may increase the serum concentration of Yohimbine. Risk C: Monitor therapy

Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy

Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination

PREGNANCY RISK FACTOR — D (show table)

LACTATION — Excretion in breast milk unknown/contraindicated

PRICING — (data from drugstore.com)
Tablets (Chlordiazepoxide-Amitriptyline)
5-12.5 mg (60): $44.99
10-25 mg (60): $65.99

Tablets (Limbitrol DS)
10-25 mg (60): $99.99

MONITORING PARAMETERS — Suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased)

CANADIAN BRAND NAMES — Limbitrol®

INTERNATIONAL BRAND NAMES — Limbatril (DE); Limbatrilin (CN); Limbitrol (AE, AT, BE, BH, BR, CY, EG, FI, FR, GH, GR, ID, IL, IQ, IR, JO, KE, KW, LB, LY, NL, OM, QA, SA, SY, TW, TZ, UG, YE, ZM); Limbitryl (IT)

MECHANISM OF ACTION — See individual agents.

PHARMACODYNAMICS / KINETICS — See individual agents.

Amitriptyline and chlordiazepoxide

Amiodarone

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amiodarone may be confused with aMILoride, amrinone
Cordarone® may be confused with Cardura®, Cordran®

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication for each new outpatient prescription and refill.
Cordarone®: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM152841.pdf
Pacerone®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088668.pdf

U.S. BRAND NAMES — Cordarone®; Pacerone®

PHARMACOLOGIC CATEGORY
Antiarrhythmic Agent, Class III

DOSING: ADULTS — Note: Lower loading and maintenance doses are preferable in women and all patients with low body weight.

Ventricular arrhythmias: Oral: 800-1600 mg/day in 1-2 doses for 1-3 weeks, then when adequate arrhythmia control is achieved, decrease to 600-800 mg/day in 1-2 doses for 1 month; maintenance: 400 mg/day; lower doses are recommended for supraventricular arrhythmias.

Breakthrough VF or VT: I.V.: 150 mg supplemental doses in 100 mL D5W over 10 minutes

Pulseless VF or VT: I.V. push: Initial: 300 mg in 20-30 mL NS or D5W; if VF or VT recurs, supplemental dose of 150 mg followed by infusion of 1 mg/minute for 6 hours, then 0.5 mg/minute (maximum daily dose: 2.2 g)

I.V. to oral therapy conversion: Use the following as a guide:
<1 week I.V. infusion: 800-1600 mg/day
1- to 3-week I.V. infusion: 600-800 mg/day
>3 week I.V. infusion: 400 mg

Recommendations for conversion to intravenous amiodarone after oral administration: During long-term amiodarone therapy (ie, ≥ 4 months), the mean plasma-elimination half-life of the active metabolite of amiodarone is 61 days. Replacement therapy may not be necessary in such patients if oral therapy is discontinued for a period <2 weeks, since any changes in serum amiodarone concentrations during this period may not be clinically significant.

Unlabeled uses:
Atrial fibrillation prophylaxis following open heart surgery (unlabeled use):Note: A variety of regimens have been used in clinical trials, including oral and intravenous regimens:
Oral: Starting in postop recovery, 400 mg twice daily for up to 7 days. Alternative regimen of amiodarone: 600 mg/day for 7 days prior to surgery, followed by 200 mg/day until hospital discharge, has also been shown to decrease the risk of postoperative atrial fibrillation. Note: A variety of regimens have been used in clinical trials.
I.V.: Starting at postop recovery, 1000 mg infused over 24 hours for 2 days has been shown to reduce the risk of postoperative atrial fibrillation. Note: A variety of regimens have been used in clinical trials.
Atrial fibrillation pharmacologic cardioversion (ACC/AHA/ESC Practice Guidelines) (unlabeled use):
Oral: Inpatient: 1.2-1.8 g/day in divided doses until 10 g total, then 200-400 mg/day maintenance. Note: Other regimens have been described and may be used clinically (Roy, 2000):
400 mg 3 times/day for 5-7 days, then 400 mg/day for 1 month, then 200 mg/day
or
10 mg/kg/day for 14 days, followed by 300 mg/day for 4 weeks, followed by maintenance dosage of 100-200 mg/day
I.V.: 5-7 mg/kg over 30-60 minutes, then 1.2-1.8 g/day continuous infusion or in divided oral doses until 10 g total. Maintenance: See oral dosing.
Recurrent atrial fibrillation (unlabeled use): No standard regimen defined; examples of regimens include: Oral: Initial: 10 mg/kg/day for 14 days; followed by 300 mg/day for 4 weeks, followed by maintenance dosage of 100-200 mg/day (Roy D, 2000). Other regimens have been described and are used clinically (ie, 400 mg 3 times/day for 5-7 days, then 400 mg/day for 1 month, then 200 mg/day).
Stable VT or SVT (unlabeled use): I.V.: First 24 hours: 1050 mg according to following regimen
Step 1: 150 mg (100 mL) over first 10 minutes (mix 3 mL in 100 mL D5W)
Step 2: 360 mg (200 mL) over next 6 hours (mix 18 mL in 500 mL D5W): 1 mg/minute
Step 3: 540 mg (300 mL) over next 18 hours: 0.5 mg/minute
Note: After the first 24 hours: 0.5 mg/minute utilizing concentration of 1-6 mg/mL

DOSING: PEDIATRIC

(For additional information see "Amiodarone: Pediatric drug information")
Arrhythmias (unlabeled use):
Loading dose: Oral: 10-20 mg/kg/day in 1-2 doses for 4-14 days or until adequate control of arrhythmia or prominent adverse effects occur; alternative loading dose in children <1 year: 600-800 mg/1.73 m2/day in 1-2 divided doses/day.
Maintenance dose: Oral: Dose may be reduced to 5 mg/kg/day for several weeks (or 200-400 mg/1.73 m2/day given once daily); if no recurrence of arrhythmia, dose may be further reduced to 2.5 mg/kg/day; maintenance doses may be given 5-7 days/week.

Arrhythmias (unlabeled use, dosing based on limited data):
Loading dose: I.V.: 5 mg/kg over 30 minutes; may repeat up to 3 times if no response.
Maintenance dose: I.V.: 2-20 mg/kg/day (5-15 mcg/kg/minute) by continuous infusion.
Note: I.V. administration at low flow rates (potentially associated with use in pediatrics) may result in leaching of plasticizers (DEHP) from intravenous tubing. DEHP may adversely affect male reproductive tract development. Alternative means of dosing and administration (1 mg/kg aliquots) may need to be considered.

Pulseless VF or VT (PALS dosing): I.V.: 5 mg/kg (maximum: 300 mg/dose) rapid I.V. bolus or I.O.; repeat up to a maximum daily dose of 15 mg/kg. (Note: Maximum recommended daily dose in adolescents is 2.2 g.)

Perfusing tachycardias (PALS dosing): I.V.: Loading dose: 5 mg/kg (maximum: 300 mg/dose) I.V. over 20-60 minutes or I.O.; may repeat up to maximum dose of 15 mg/kg/day. (Note: Maximum recommended daily dose in adolescents is 2.2 g.)

DOSING: ELDERLY — Refer to adult dosing. No specific guidelines available. Dose selection should be cautious, at low end of dosage range, and titration should be slower to evaluate response.

DOSING: RENAL IMPAIRMENT — Hemodialysis effects: Not removed by hemodialysis or peritoneal dialysis (0% to 5%); no supplemental doses required.

DOSING: HEPATIC IMPAIRMENT — Dosage adjustment is probably necessary in substantial hepatic impairment. No specific guidelines available. If hepatic enzymes exceed 3 times normal or double in a patient with an elevated baseline, consider decreasing the dose or discontinuing amiodarone.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution, as hydrochloride: 50 mg/mL (3 mL, 9 mL, 18 mL) [contains benzyl alcohol and polysorbate 80]

Tablet, as hydrochloride [scored]: 200 mg, 400 mg
Cordarone®: 200 mg
Pacerone®: 100 mg [not scored], 200 mg, 400 mg

DOSAGE FORMS: CONCISE
Injection, solution: 50 mg/mL (3 mL, 9 mL, 18 mL)

Tablet [scored]: 200 mg, 400 mg
Cordarone®: 200 mg
Pacerone®: 100 mg [not scored], 200 mg, 400 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION
Oral: Administer consistently with regard to meals. Take in divided doses with meals if high daily dose or if GI upset occurs. If GI intolerance occurs with single-dose therapy, use twice daily dosing.

I.V.: For infusions >1 hour, use concentrations ≤ 2 mg/mL unless a central venous catheter is used. Use only volumetric infusion pump; use of drop counting may lead to underdosing. Administer through I.V. line with in-line filter.

Adjust administration rate to urgency (give more slowly when perfusing arrhythmia present). Slow the infusion rate if hypotension or bradycardia develops. Infusions >2 hours must be administered in glass or polyolefin bottles. Note: I.V. administration at lower flow rates (potentially associated with use in pediatrics) and higher concentrations than recommended may result in leaching of plasticizers (DEHP) from intravenous tubing. DEHP may adversely affect male reproductive tract development. Alternative means of dosing and administration (1 mg/kg aliquots) may need to be considered.

COMPATIBILITY — Variable stability (consult detailed reference): D5W, NS.

Y-site administration:
Compatible: Amikacin, ceftizoxime, ceftriaxone, cefuroxime, clarithromycin, clindamycin, dobutamine, dopamine, doxycycline, erythromycin lactobionate, esmolol, gentamicin, insulin (regular), isoproterenol, labetalol, lidocaine, metaraminol, metronidazole, midazolam, morphine, nitroglycerin, norepinephrine, penicillin G potassium, phentolamine, phenylephrine, potassium chloride, procainamide, tobramycin, vancomycin. Incompatible: Aminophylline, cefamandole, heparin, sodium bicarbonate.
Variable (consult detailed reference): Cefazolin.
Visually Compatible (Chalmers, 2001): Amphotericin B, atracurium, atropine, calcium chloride, calcium gluconate, ciprofloxacin, epinephrine, eptifibatide, famotidine, fentanyl citrate, fluconazole, furosemide (1 mg/mL), lepirudin, lorazepam, magnesium sulfate (20 mg/mL), methylprednisolone sodium succinate, milrinone, sodium nitroprusside, tirofiban, vasopressin, vecuronium. Visually Incompatible: Ampicillin-sulbactam, ceftazidime, digoxin, furosemide (10 mg/mL), imipenem-cilastatin, magnesium sulfate (500 mg/mL), piperacillin, piperacillin-tazobactam, potassium phosphate, sodium phosphate.

Compatibility in syringe: Incompatible: Heparin.

Compatibility when admixed: Compatible: Dobutamine, lidocaine, potassium chloride, procainamide, propafenone, verapamil. Variable (consult detailed reference): Furosemide, quinidine.

USE — Management of life-threatening recurrent ventricular fibrillation (VF) or hemodynamically-unstable ventricular tachycardia (VT) refractory to other antiarrhythmic agents or in patients intolerant of other agents used for these conditions

USE - UNLABELED / INVESTIGATIONAL
Cardiac arrest with persistent ventricular tachycardia (VT) or ventricular fibrillation (VF) if defibrillation, CPR, and vasopressor administration have failed (ACLS/PALS guidelines)

Control of hemodynamically-stable VT, polymorphic VT with a normal baseline QT interval, or wide-complex tachycardia of uncertain origin (ACLS/PALS guidelines)

Control of rapid ventricular rate due to accessory pathway conduction in pre-excited atrial arrhythmias (ACLS guidelines)

Heart rate control in patients with atrial fibrillation and heart failure [no accessory pathway] (ACC/AHA/ESC Practice Guidelines)

Paroxysmal supraventricular tachycardia (SVT)

Prevention of postoperative atrial fibrillation associated with cardiothoracic surgery

Pharmacologic adjunct to ICD therapy to suppress symptomatic ventricular tachyarrhythmias in otherwise optimally-treated patients with heart failure (ACC/AHA/ESC Practice Guidelines)

Pharmacologic conversion of atrial fibrillation to normal sinus rhythm; maintenance of normal sinus rhythm

ADVERSE REACTIONS SIGNIFICANT — In a recent meta-analysis, patients taking lower doses of amiodarone (152-330 mg daily for at least 12 months) were more likely to develop thyroid, neurologic, skin, ocular, and bradycardic abnormalities than those taking placebo (Vorperian, 1997). Pulmonary toxicity was similar in both the low dose amiodarone group and in the placebo group but there was a trend towards increased toxicity in the amiodarone group. Gastrointestinal and hepatic events were seen to a similar extent in both the low dose amiodarone group and placebo group. As the frequency of adverse events varies considerably across studies as a function of route and dose, a consolidation of adverse event rates is provided by Goldschlager, 2000.
Cardiovascular: Hypotension (I.V. 16%, refractory in rare cases)
Central nervous system (3% to 40%): Abnormal gait/ataxia, dizziness, fatigue, headache, malaise, impaired memory, involuntary movement, insomnia, poor coordination, peripheral neuropathy, sleep disturbances, tremor
Dermatologic: Photosensitivity (10% to 75%)
Endocrine & Metabolic: Hypothyroidism (1% to 22%)
Gastrointestinal: Nausea, vomiting, anorexia, and constipation (10% to 33%)
Hepatic: AST or ALT level >2x normal (15% to 50%)
Ocular: Corneal microdeposits (>90%; causes visual disturbance in <10%)

1% to 10%:
Cardiovascular: CHF (3%), bradycardia (3% to 5%), AV block (5%), conduction abnormalities, SA node dysfunction (1% to 3%), cardiac arrhythmia, flushing, edema. Additional effects associated with I.V. administration include asystole, cardiac arrest, electromechanical dissociation, ventricular tachycardia, and cardiogenic shock.
Dermatologic: Slate blue skin discoloration (<10%)
Endocrine & metabolic: Hyperthyroidism (3% to 10%; more common in iodine-deficient regions of the world), libido decreased
Gastrointestinal: Abdominal pain, abnormal salivation, abnormal taste (oral)
Hematologic: Coagulation abnormalities
Hepatic: Hepatitis and cirrhosis (<3%)
Local: Phlebitis (I.V., with concentrations >3 mg/mL)
Ocular: Visual disturbances (2% to 9%), halo vision (<5% occurring especially at night), optic neuritis (1%)
Respiratory: Pulmonary toxicity has been estimated to occur at a frequency between 2% and 7% of patients (some reports indicate a frequency as high as 17%). Toxicity may present as hypersensitivity pneumonitis; pulmonary fibrosis (cough, fever, malaise); pulmonary inflammation; interstitial pneumonitis; or alveolar pneumonitis. ARDS has been reported in up to 2% of patients receiving amiodarone, and postoperatively in patients receiving oral amiodarone.
Miscellaneous: Abnormal smell (oral)

<1% (Limited to important or life-threatening): Acute intracranial hypertension (I.V.), acute renal failure, agranulocytosis, alopecia, anaphylactic shock, angioedema, aplastic anemia, bone marrow granuloma, bronchiolitis obliterans organizing pneumonia (BOOP), bronchospasm, confusion, disorientation, dyspnea, encephalopathy, epididymitis (noninfectious), erectile dysfunction, erythema multiforme, exfoliative dermatitis, hallucination, hemolytic anemia, hemoptysis, hyperglycemia, hypertriglyceridemia, hypotension (oral), hypoxia, impotence, injection site reactions, leukocytoclastic vasculitis, muscle weakness, myopathy, neutropenia, optic neuropathy, pancreatitis, pancytopenia, parkinsonian symptoms, photophobia, pleuritis, proarrhythmia, pruritus, pseudotumor cerebri, pulmonary alveolar hemorrhage, pulmonary edema, pulmonary mass, QT interval increased, rash, renal impairment, renal insufficiency, respiratory failure, rhabdomyolysis, SIADH, sinus arrest, spontaneous ecchymosis, Stevens-Johnson syndrome, thrombocytopenia, thyroid nodules, thyroid cancer, thyrotoxicosis, torsade de pointes (rare), toxic epidermal necrolysis, urticaria, vasculitis, ventricular fibrillation, wheezing

CONTRAINDICATIONS — Hypersensitivity to amiodarone, iodine, or any component of the formulation; severe sinus-node dysfunction; second- and third-degree heart block (except in patients with a functioning artificial pacemaker); bradycardia causing syncope (except in patients with a functioning artificial pacemaker); cardiogenic shock; pregnancy

WARNINGS / PRECAUTIONS
Boxed warnings: Arrhythmias: Appropriate use: See "Disease-related concerns" below. Hepatotoxicity: See "Concerns related to adverse effects" below. Proarrhythmic effect: See "Concerns related to adverse effects" below. Pulmonary toxicity: See "Concerns related to adverse effects" below.

Concerns related to adverse effects: Bradycardia/hypotension: May cause hypotension and bradycardia (infusion-rate related). Hepatotoxicity: [U.S. Boxed Warning]: Liver toxicity is common, but usually mild with evidence of increased liver enzymes; severe liver toxicity can occur and has been fatal in a few cases. Optic neuritis/neuropathy: May cause optic neuropathy and/or optic neuritis, usually resulting in visual impairment. Corneal microdeposits occur in a majority of patients, and may cause visual disturbances in some patients (blurred vision, halos); these are not generally considered a reason to discontinue treatment. Corneal refractive laser surgery is generally contraindicated in amiodarone users (from manufacturers of surgical devices). Photosensitivity: Avoid excessive exposure to sunlight; may cause photosensitivity. Proarrhythmic effect: [U.S. Boxed Warning]: Amiodarone can exacerbate arrhythmias, by making them more difficult to tolerate or reverse; other types of arrhythmias have occurred, including significant heart block, sinus bradycardia new ventricular fibrillation, incessant ventricular tachycardia, increased resistance to cardioversion, and polymorphic ventricular tachycardia associated with QTc prolongation (torsade de pointes [TdP]). Risk may be increased with concomitant use of other antiarrhythmic agents or drugs that prolong the QTc interval. Proarrhythmic effects may be prolonged. Pulmonary toxicity: [U.S. Boxed Warning]: Lung damage (abnormal diffusion capacity) may occur without symptoms; monitor for pulmonary toxicity (eg, chronic interstitial pneumonitis, organizing pneumonia, acute respiratory distress syndrome, solitary pulmonary mass). Educate patients about monitoring for symptoms (eg, nonproductive cough, dyspnea, pleuritic pain, weight loss, fever, malaise). Evaluate new respiratory symptoms; pre-existing pulmonary disease does not increase risk of developing pulmonary toxicity, but if pulmonary toxicity develops then the prognosis is worse. Use of lower doses may be associated with a decreased incidence, but pulmonary toxicity has been reported in patients treated with low doses. The lowest effective dose should be used as appropriate for the acuity/severity of the arrhythmia being treated.

Disease-related concerns: Arrhythmias: Appropriate use: [U.S. Boxed Warnings]: Only indicated for patients with life-threatening arrhythmias because of risk of toxicity. Alternative therapies should be tried first before using amiodarone. Patients should be hospitalized when amiodarone is initiated. Currently, the 2005 ACLS guidelines recommend I.V. amiodarone as the preferred antiarrhythmic for the treatment of pulseless VT/VF, both life-threatening arrhythmias. In patients with non-life-threatening arrhythmias (eg, atrial fibrillation), amiodarone should be used only if the use of other antiarrhythmics has proven ineffective or are contraindicated. Cardiac devices (eg, implanted defibrillators, pacemakers): Chronic administration of antiarrhythmic drugs may affect defibrillation or pacing thresholds. Assess when initiating amiodarone and during therapy. Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy. Hepatic impairment: Use with caution in patients with hepatic impairment. Thyroid disease: Use very cautiously and with close monitoring in patients with thyroid disease; may cause hyper- or hypothyroidism. Hyperthyroidism may result in thyrotoxicosis and may aggravate or cause breakthrough arrhythmias. If any new signs of arrhythmia appear, hyperthyroidism should be considered. Thyroid function should be monitored prior to treatment and periodically thereafter, particularly in the elderly and in patients with underlying thyroid dysfunction.

Concurrent drug therapy issues: Drugs metabolized by CYP enzymes: Amiodarone is a potent inhibitor of CYP enzymes and transport proteins (including p-glycoprotein), which may lead to increased serum concentrations/toxicity of a number of medications. Drugs with QT prolongation potential: Particular caution must be used when a drug with QTc-prolonging potential relies on metabolism via enzymes amiodarone inhibits, since the effect of elevated concentrations may be additive with the effect of amiodarone. Carefully assess risk:benefit of coadministration of other drugs which may prolong QTc interval.

Special populations: Elderly: Monitor thyroid function prior to treatment and periodically thereafter. Pediatrics: Safety and efficacy have not been fully established in children. Surgical patients: Caution in surgical patients; may enhance hemodynamic effect of anesthetics; associated with increased risk of adult respiratory distress syndrome (ARDS) postoperatively.

Dosage form specific issues: Benzyl alcohol: Injection contains benzyl alcohol which has been associated with "gasping syndrome" in neonates.

Other warnings/precautions: CAST trial: In the Cardiac Arrhythmia Suppression Trial (CAST), recent (>6 days but <2 years ago) myocardial infarction patients with asymptomatic, nonlife-threatening ventricular arrhythmias did not benefit and may have been harmed by attempts to suppress the arrhythmia with flecainide or encainide. An increased mortality or nonfatal cardiac arrest rate (7.7%) was seen in the active treatment group compared with patients in the placebo group (3%). The applicability of the CAST results to other populations is unknown. Use of amiodarone post-MI was not associated with an increase in mortality in two post-MI trials. Antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias. Discontinuation of therapy: Patients may still be at risk for amiodarone"related drug interactions after the drug has been discontinued. The pharmacokinetics are complex (due to prolonged duration of action and half-life) and difficult to predict.

METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (minor), 2C8 (major at low concentration), 2C19 (minor), 2D6 (minor), 3A4 (major); Inhibits CYP1A2 (weak), 2A6 (moderate), 2B6 (weak), 2C9 (moderate), 2C19 (weak), 2D6 (moderate), 3A4 (moderate)

DRUG INTERACTIONS
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Antiarrhythmic Agents (Class Ia): May enhance the QTc-prolonging effect of Amiodarone. Amiodarone may increase the metabolism of Antiarrhythmic Agents (Class Ia). Risk D: Consider therapy modification

Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Azithromycin: May enhance the QTc-prolonging effect of Amiodarone. Risk D: Consider therapy modification

Beta-Blockers: Amiodarone may enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the bioavailability of Amiodarone. Risk D: Consider therapy modification

Calcium Channel Blockers (Nondihydropyridine): May enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported. Risk D: Consider therapy modification

Cardiac Glycosides: Amiodarone may increase the serum concentration of Cardiac Glycosides. Risk D: Consider therapy modification

Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Cimetidine: May decrease the metabolism of Amiodarone. Consider using an alternative H2 antagonist. Risk D: Consider therapy modification

Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy

Colchicine: P-Glycoprotein Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification

Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification

CycloSPORINE: Amiodarone may decrease the metabolism of CycloSPORINE. Risk D: Consider therapy modification

CYP2A6 Substrates: CYP2A6 Inhibitors (Moderate) may decrease the metabolism of CYP2A6 Substrates. Risk C: Monitor therapy

CYP2C8 Inducers (Highly Effective): May increase the metabolism of CYP2C8 Substrates (High risk). Risk C: Monitor therapy

CYP2C8 Inhibitors (Moderate): May decrease the metabolism of CYP2C8 Substrates (High risk). Risk C: Monitor therapy

CYP2C8 Inhibitors (Strong): May decrease the metabolism of CYP2C8 Substrates (High risk). Risk D: Consider therapy modification

CYP2C9 Substrates (High risk): CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy

(For additional information see "Amiodarone: Patient drug information" and see "Amiodarone: Pediatric drug information")

CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification

CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

Dabigatran Etexilate: Amiodarone may increase the serum concentration of Dabigatran Etexilate. Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Deferasirox: May increase the serum concentration of CYP2C8 Substrates (High risk). Risk C: Monitor therapy

Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination

Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: A lower starting dose of eplerenone (25 mg once daily) is recommended in patients with hypertension who are also taking drugs that are moderate inhibitors of CYP3A4. Risk D: Consider therapy modification

Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Risk X: Avoid combination

FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Risk D: Consider therapy modification

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

Flecainide: Amiodarone may decrease the metabolism of Flecainide. Risk D: Consider therapy modification

Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification

Grapefruit Juice: May decrease serum concentrations of the active metabolite(s) of Amiodarone. Grapefruit Juice may increase the serum concentration of Amiodarone. Risk X: Avoid combination

Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

HMG-CoA Reductase Inhibitors: Amiodarone may decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Dose of HMG-CoA reductase inhibitor may need to be reduced (e.g., simvastatin prescribing information recommends not exceeding 20 mg/day during concurrent therapy). Exceptions: Pravastatin. Risk D: Consider therapy modification

Lidocaine: Amiodarone may decrease the metabolism of Lidocaine. Risk C: Monitor therapy

Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Orlistat: May decrease the absorption of Amiodarone. Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

P-Glycoprotein Substrates: P-Glycoprotein Inhibitors may increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Phenytoin: May increase the metabolism of Amiodarone. Amiodarone may decrease the metabolism of Phenytoin. Risk C: Monitor therapy

Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy

Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination

Protease Inhibitors: May decrease the metabolism of Amiodarone. Risk X: Avoid combination

QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification

QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Rifamycin Derivatives: May increase the metabolism of Amiodarone. Risk C: Monitor therapy

Rivaroxaban: P-Glycoprotein Inhibitors may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy

Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy

Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Risk C: Monitor therapy

Silodosin: P-Glycoprotein Inhibitors may increase the serum concentration of Silodosin. Risk X: Avoid combination

Sodium Iodide I131: Amiodarone may diminish the therapeutic effect of Sodium Iodide I131. Risk D: Consider therapy modification

Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk D: Consider therapy modification

Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination

Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination

Topotecan: P-Glycoprotein Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Amiodarone may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination

ETHANOL / NUTRITION / HERB INTERACTIONS
Food: Increases the rate and extent of absorption of amiodarone. Grapefruit juice increases bioavailability of oral amiodarone by 50% and decreases the conversion of amiodarone to N-DEA (active metabolite); altered effects are possible; use should be avoided during therapy.

Herb/Nutraceutical: St John's wort may decrease amiodarone levels or enhance photosensitization. Avoid ephedra (may worsen arrhythmia). Avoid dong quai.

PREGNANCY RISK FACTOR — D (show table)

PREGNANCY IMPLICATIONS — May cause fetal harm when administered to a pregnant woman, leading to congenital goiter and hypo- or hyperthyroidism.

LACTATION — Enters breast milk/not recommended (AAP rates "of concern")

BREAST-FEEDING CONSIDERATIONS — Hypothyroidism may occur in nursing infants. Both amiodarone and its active metabolite are excreted in human milk. Breast-feeding may lead to significant infant exposure and potential toxicity.

DIETARY CONSIDERATIONS — Administer consistently with regard to meals. Amiodarone is a potential source of large amounts of inorganic iodine; ~3 mg of inorganic iodine per 100 mg of amiodarone is released into the systemic circulation. Recommended daily allowance for iodine in adults is 150 mcg.

Grapefruit juice is not recommended.

PRICING — (data from drugstore.com)
Tablets (Amiodarone HCl)
200 mg (30): $28.99

Tablets (Cordarone)
200 mg (60): $272.01

Tablets (Pacerone)
100 mg (30): $147.29

MONITORING PARAMETERS — Blood pressure, heart rate (ECG) and rhythm throughout therapy; assess patient for signs of lethargy, edema of the hands or feet, weight loss, and pulmonary toxicity (baseline pulmonary function tests); liver function tests; monitor serum electrolytes, especially potassium and magnesium. Assess thyroid function tests before initiation of treatment and then periodically thereafter (some experts suggest every 3-6 months). If signs or symptoms of thyroid disease or arrhythmia breakthrough/exacerbation occur then immediate re-evaluation is necessary. Amiodarone partially inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3); serum T4 and reverse triiodothyronine (rT3) concentrations may be increased and serum T3 may be decreased; most patients remain clinically euthyroid, however, clinical hypothyroidism or hyperthyroidism may occur.

Perform regular ophthalmic exams.

Patients with implantable cardiac devices: Monitor pacing or defibrillation thresholds with initiation of amiodarone and during treatment.

REFERENCE RANGE — Therapeutic: 0.5-2.5 mg/L (SI: 1-4 µmol/L) (parent); desethyl metabolite is active and is present in equal concentration to parent drug

CANADIAN BRAND NAMES — Alti-Amiodarone; Amiodarone Hydrochloride for Injection®; Apo-Amiodarone®; Cordarone®; Dom-Amiodarone; Gen-Amiodarone; Mylan-Amiodarone; Novo-Amiodarone; PHL-Amiodarone; PMS-Amiodarone; PRO-Amiodarone; ratio-Amiodarone; ratio-Amiodarone I.V.; Riva-Amiodarone; Sandoz-Amiodarone

INTERNATIONAL BRAND NAMES — Aldarin (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Aldarone (TH); Amicordin (PL); Amiocar (AR); Amiodacore (IL); Amiodarex (DE); Amiodarona (CN); Amiohexal (DE); Amiokordin (PL); Ancaron (JP); Angiodarona (BR); Angoron (GR); Anoion (PH); Aratac (AU, MY, SG, TH, TW); Arycor (CO); Atlansil (AR, BR, CN, EC, PE, UY); Braxan (MX); Cardilor (MY, TH); Cardinorm (AU); Coedarone (MX); Corbionax (FR); Cordarex (DE); Cordarone (AE, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CL, CR, CY, CZ, DO, EC, EE, EG, ET, FI, FR, GH, GM, GN, GT, GY, HK, HN, ID, IL, IQ, IR, IT, JM, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, NI, NL, NO, OM, PA, PE, PH, PK, PL, PT, PY, QA, SA, SC, SD, SE, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, YE, ZA, ZM, ZW); Cordarone X (AU, GB, IE, IN, ZA); Coronovo (AR); Diarona (UY); Escodaron (CH); Eurythmic (IN); Forken (MX); Hexarone (ZA); Kendaron (ID); Keritmon (MX); Miodar (DO); Opacorden (PL); Procor (IL); Rithmik (AU); Sedacoron (AT, HK, PL, TW); Tachydaron (DE); Tiaryt (ID); Trangorex (ES, VE)

MECHANISM OF ACTION — Class III antiarrhythmic agent which inhibits adrenergic stimulation (alpha- and beta-blocking properties), affects sodium, potassium, and calcium channels, prolongs the action potential and refractory period in myocardial tissue; decreases AV conduction and sinus node function

PHARMACODYNAMICS / KINETICS
Absorption: Slow and variable

Onset of action: Oral: 2 days to 3 weeks; I.V.: May be more rapid
Peak effect: 1 week to 5 months

Duration after discontinuing therapy: 7-50 days
Note: Mean onset of effect and duration after discontinuation may be shorter in children than adults

Distribution: Vd: 66 L/kg (range: 18-148 L/kg)

Protein binding: 96%

Metabolism: Hepatic via CYP2C8 and 3A4 to active N-desethylamiodarone metabolite; possible enterohepatic recirculation

Bioavailability: Oral: 35% to 65%

Half-life elimination: Terminal: 40-55 days (range: 26-107 days); shorter in children

Time to peak, serum: 3-7 hours

Excretion: Feces; urine (<1% as unchanged drug)

PATIENT INFORMATION — Take with food; use sunscreen or stay out of sun to prevent burns; skin discoloration is reversible; photophobia may make sunglasses necessary; do not discontinue abruptly; regular blood work for thyroid functions tests and ophthalmologic exams are necessary; notify prescriber if persistent dry cough or shortness of breath occurs

Aminophylline

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Aminophylline may be confused with amitriptyline, ampicillin

PHARMACOLOGIC CATEGORY
Theophylline Derivative

DOSING: ADULTS
Treatment of acute bronchospasm: I.V.:
Loading dose (in patients not currently receiving aminophylline or theophylline): 6 mg/kg (based on aminophylline) administered I.V. over 20-30 minutes; administration rate should not exceed 25 mg/minute (aminophylline)
Approximate I.V. maintenance dosages: Based upon continuous infusions; bolus dosing may be determined by multiplying the hourly infusion rate by 24 hours and dividing by the desired number of doses/day
Smoker: 0.8 mg/kg/hour
Nonsmoker: 0.5 mg/kg/hour
Older patients and patients with cor pulmonale: 0.3 mg/kg/hour
Patients with congestive heart failure: 0.1-0.2 mg/kg/hour
Dosage should be adjusted according to serum level measurements during the first 12- to 24-hour period.

Reversal of adenosine-, dipyridamole-, or regadenoson-induced adverse reactions (eg, angina, hypotension) during nuclear cardiac stress testing (unlabeled use): I.V.: 50-250 mg administered over 30-60 seconds, repeat as necessary
Note: Since adenosine-induced side effects are short lived after discontinuation of the infusion, aminophylline administration is only very rarely required.

Bronchodilator: Oral: Initial: 380 mg/day (equivalent to theophylline 300 mg/day) in divided doses every 6-8 hours; may increase dose after 3 days; maximum dose: 928 mg/day (equivalent to theophylline 800 mg/day)

DOSING: PEDIATRIC

(For additional information see "Aminophylline: Pediatric drug information")
Treatment of acute bronchospasm: I.V.:
Loading dose: Patients not currently receiving aminophylline or theophylline: 6 mg/kg (based on aminophylline) administered I.V. over 20-30 minutes; administration rate should not exceed 25 mg/minute (aminophylline)
Approximate I.V. maintenance dosages: Based upon continuous infusions; bolus dosing (often used in children <6 months of age) may be determined by multiplying the hourly infusion rate by 24 hours and dividing by the desired number of doses/day
6 weeks to 6 months: 0.5 mg/kg/hour
6 months to 1 year: 0.6-0.7 mg/kg/hour
1-9 years: 1 mg/kg/hour
9-16 years: Refer to adult dosing.
Dosage should be adjusted according to serum level measurements during the first 12- to 24-hour period.

Bronchodilator: Oral: Children ≥ 45 kg: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution, as dihydrate: 25 mg/mL (10 mL, 20 mL)

Injection, solution, as dihydrate [preservative free]: 25 mg/mL (10 mL, 20 mL)

Tablet, as dihydrate: 100 mg

DOSAGE FORMS: CONCISE
Injection, solution: 25 mg/mL (10 mL, 20 mL)

Injection, solution, [preservative free]: 25 mg/mL (10 mL, 20 mL)

Tablet: 100 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Dilute with I.V. fluid to a concentration of 1 mg/mL and infuse over 20-30 minutes; maximum concentration: 25 mg/mL; maximum rate of infusion: 0.36 mg/kg/minute, and no greater than 25 mg/minute. I.M. administration is not recommended. Oral and I.V. should be administered around-the-clock rather than 4 times/day, 3 times/day, etc (eg, 12-6-12-6, not 9-1-5-9) to promote less variation in peak and trough serum levels.

For reversal of adenosine-, dipyridamole-, or regadenoson-induced adverse events during nuclear cardiac stress testing, administer I.V. undiluted over 30-60 seconds, repeat as necessary. Since adenosine-induced side effects are short lived after discontinuation of the infusion, aminophylline administration is only very rarely required.

COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, D20W, LR, 1/2NS, NS; variable stability (consult detailed reference) in fat emulsion 10%.

Y-site administration: Compatible: Allopurinol, amifostine, amphotericin B cholesteryl sulfate complex, aztreonam, ceftazidime, cimetidine, cladribine, docetaxel, doxorubicin liposome, enalaprilat, esmolol, etoposide, famotidine, filgrastim, fluconazole, fludarabine, foscarnet, gatifloxacin, gemcitabine, granisetron, heparin with hydrocortisone sodium succinate, inamrinone, labetalol, levofloxacin, linezolid, melphalan, meropenem, morphine, paclitaxel, pancuronium, piperacillin/tazobactam, potassium chloride, propofol, ranitidine, remifentanil, sargramostim, tacrolimus, teniposide, thiotepa, tolazoline, vecuronium, vitamin B complex with C. Incompatible: Amiodarone, ciprofloxacin, clarithromycin, dobutamine, hydralazine, ondansetron, vinorelbine, warfarin. Variable (consult detailed reference): Cisatracurium, diltiazem.

Compatibility in syringe: Compatible: Heparin, metoclopramide, pentobarbital, thiopental. Incompatible: Doxapram.

Compatibility when admixed: Compatible: Amobarbital, bretylium, calcium gluconate, chloramphenicol, cimetidine, dexamethasone, diphenhydramine, dopamine, erythromycin lactobionate, esmolol, floxacillin, flumazenil, furosemide, heparin, hydrocortisone sodium succinate, lidocaine, mephentermine, meropenem, methyldopate, metronidazole with sodium bicarbonate, nitroglycerin, pentobarbital, phenobarbital, potassium chloride, ranitidine, sodium bicarbonate, terbutaline. Incompatible: Atracurium, bleomycin, cefepime, ceftazidime, ceftriaxone, chlorpromazine, ciprofloxacin, clindamycin, dobutamine, doxorubicin, epinephrine, hydralazine, hydrocortisone sodium succinate with cephalothin sodium, hydroxyzine, insulin (regular), isoproterenol, levorphanol, meperidine, morphine, norepinephrine, papaverine with trimecaine, penicillin G potassium, pentazocine, prochlorperazine edisylate, prochlorperazine mesylate, promazine, promethazine, vitamin B complex with C. Variable (consult detailed reference): Amikacin, ascorbic acid, corticotropin, dimenhydrinate, methylprednisolone sodium succinate, nafcillin, procaine, vancomycin, verapamil, zinc.

USE — Bronchodilator in reversible airway obstruction due to asthma or COPD; increase diaphragmatic contractility

USE - UNLABELED / INVESTIGATIONAL — Reversal of adenosine-, dipyridamole-, or regadenoson-induced adverse reactions (eg, angina, hypotension) during nuclear cardiac stress testing

ADVERSE REACTIONS SIGNIFICANT
Uncommon at serum theophylline concentrations ≤ 15 mcg / mL

1% to 10%:
Cardiovascular: Tachycardia
Central nervous system: Nervousness, restlessness
Gastrointestinal: Nausea, vomiting

<1% (Limited to important or life-threatening): Allergic reactions, gastric irritation, insomnia, irritability, skin rash, seizure, tremor

CONTRAINDICATIONS — Hypersensitivity to theophylline, ethylenediamine, or any component of the formulation

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Theophylline toxicity: If a patient develops signs and symptoms of theophylline toxicity (eg, persistent, repetitive vomiting), a serum level should be measured and subsequent doses held.

Disease-related concerns: Cardiovascular disease: Use with caution in patients with hypertension or cardiac arrhythmias (excluding bradyarrhythmias). Hyperthyroidism: Use with caution in patients with hyperthyroidism. Peptic ulcer disease: Use with caution in patient with peptic ulcer disease. Seizure disorder: Use with caution in patients with a history of seizure disorder.

Other warnings/precautions: Dosage adjustments: Due to potential saturation of theophylline clearance at serum levels within (or in some patients less than) the therapeutic range, dosage adjustment should be made in small increments (maximum: 25% reduction). Monitoring: Due to wide interpatient variability, theophylline serum level measurements must be used to optimize therapy and prevent serious toxicity.

METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2E1 (minor), 3A4 (minor)

DRUG INTERACTIONS
Adenosine: Theophylline Derivatives may diminish the therapeutic effect of Adenosine. Risk D: Consider therapy modification

Allopurinol: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Aminoglutethimide: May increase the metabolism of Theophylline Derivatives. Risk C: Monitor therapy

Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Theophylline Derivatives. Risk C: Monitor therapy

Benzodiazepines: Theophylline Derivatives may diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Theophylline Derivatives. This is true at higher beta-blockers doses where cardioselectivity is lost. Risk C: Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Theophylline Derivatives. Risk D: Consider therapy modification

Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Theophylline Derivatives. Risk C: Monitor therapy

Cimetidine: May decrease the metabolism of Theophylline Derivatives. Risk D: Consider therapy modification

CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy

CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification

Disulfiram: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Febuxostat: May increase the serum concentration of Theophylline Derivatives. Risk X: Avoid combination

Fluvoxamine: May decrease the metabolism of Theophylline Derivatives. Risk D: Consider therapy modification

Interferons: May decrease the metabolism of Theophylline Derivatives. Risk C: Monitor therapy

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination

Isoniazid: May decrease the metabolism of Theophylline Derivatives. Risk D: Consider therapy modification

Lithium: Theophylline Derivatives may increase the excretion of Lithium. Risk C: Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of Theophylline Derivatives. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin; Telithromycin. Risk D: Consider therapy modification

Mexiletine: May decrease the metabolism of Theophylline Derivatives. Risk D: Consider therapy modification

Moricizine: May increase the metabolism of Theophylline Derivatives. Risk C: Monitor therapy

Pentoxifylline: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Phenytoin: May increase the metabolism of Theophylline Derivatives. Theophylline Derivatives may decrease the serum concentration of Phenytoin. Risk C: Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Theophylline Derivatives. Exceptions: Amprenavir; Fosamprenavir. Risk C: Monitor therapy

QuiNINE: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Quinolone Antibiotics: May decrease the metabolism of Theophylline Derivatives. Ciprofloxacin and enoxacin are of greatest concern. Theophylline/quinolone therapy might augment the seizure-producing potential of each of the individual agents. Exceptions: Gatifloxacin; Gemifloxacin; Levofloxacin; Lomefloxacin; Moxifloxacin; Nalidixic Acid; Sparfloxacin; Trovafloxacin. Risk D: Consider therapy modification

Regadenoson: Aminophylline may diminish the vasodilatory effect of Regadenoson. Risk D: Consider therapy modification

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tacrine: May decrease the metabolism of Theophylline Derivatives. Risk C: Monitor therapy

Thiabendazole: May decrease the metabolism of Theophylline Derivatives. Risk D: Consider therapy modification

Thyroid Products: May increase the metabolism of Theophylline Derivatives. Risk C: Monitor therapy

Ticlopidine: May decrease the metabolism of Theophylline Derivatives. Risk C: Monitor therapy

Zafirlukast: Theophylline Derivatives may decrease the serum concentration of Zafirlukast. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Food does not appreciably affect absorption. Avoid extremes of dietary protein and carbohydrate intake. Changes in diet may affect the elimination of theophylline; charcoal-broiled foods may increase elimination, reducing half-life by 50%.

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Theophylline crosses the placenta; adverse effects may be seen in the newborn. Theophylline metabolism may change during pregnancy; monitor serum levels.

LACTATION — Enters breast milk/compatible (AAP rates "compatible")

BREAST-FEEDING CONSIDERATIONS — Irritability may be observed in the nursing infant.

PRICING — (data from drugstore.com)
Tablets (Aminophylline)
100 mg (30): $12.99
200 mg (90): $19.00

CANADIAN BRAND NAMES — Phyllocontin®; Phyllocontin®-350

INTERNATIONAL BRAND NAMES — Aminocont (FI); Aminofilina (EC, GT, PL); Aminomal (CH, CZ, IT); Aminophyllin (HR, NO); Aminophylline Renaudin (FR); Aminophyllinum (PL); Aminophyllinum Prolongatum (PL); Aminophyllinum Retard (HU, PL); Aminoslow (LU); Anephyllin (JP); Asiphylline (TW); Asthcontin (KP); Cardiomin (CN); Cardirenal (AR); Cardophyllin (AU); Carine (AU); Clonofillin SR (HU); Diaphyllin (HU); Escophyllin (CH); Eufilina (ES); Eufilina Mite (PT); Eufilina Venosa (ES); Euphyllin (AT, BE, BG, CH, CZ, DE, LU, NL); Euphyllin Retard (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Godafilin (ES); Kyophyllin (JP); Minophyl (IN); Neophyllin (SG); Pediatric Asthcontin for Children SR (KP); Peterphyllin (ZA); Pharmafil (MX); Phyllocontin (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GB, GH, GM, GN, GY, IE, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, PK, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TW, TZ, UG, YE, ZA, ZM, ZW); Phyllocontin Continus (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Phyllotemp (CH, DE, GR); Planphylline (FR); Retafilin (HR); Tefamin (IT); Teofylamin (DK); Teofyllamin Ipex (SE); Unifilin (BR)

MECHANISM OF ACTION — Causes bronchodilatation, diuresis, CNS and cardiac stimulation, and gastric acid secretion by blocking phosphodiesterase which increases tissue concentrations of cyclic adenine monophosphate (cAMP) which in turn promote catecholamine stimulation of lipolysis, glycogenolysis, and gluconeogenesis and induce release of epinephrine from adrenal medulla cells

PHARMACODYNAMICS / KINETICS
Theophylline:

Absorption: Oral: Dosage form dependent

Distribution: 0.45 L/kg based on ideal body weight

Protein binding: 40%, primarily to albumin

Metabolism: Children >1 year and Adults: Hepatic; involves CYP1A2, 2E1, and 3A4; forms active metabolites (caffeine and 3-methylxanthine)

Half-life elimination: Highly variable and dependent upon age, liver function, cardiac function, lung disease, and smoking history

Time to peak, serum:
Oral: Immediate release: 1-2 hours
I.V.: Within 30 minutes

Excretion: Children >3 months and Adults: Urine (10% as unchanged drug)

PATIENT INFORMATION — Do not drink or eat large quantities of caffeine-containing beverages or food (colas, coffee, chocolate).

Pages

Sunday, July 4, 2010

Amitriptyline and chlordiazepoxide

Amitriptyline and chlordiazepoxide

Amiodarone

Aminophylline