(pro PAF en one)
Treatment of life-threatening ventricular arrhythmias; to prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) or paroxysmal supraventricular tachycardia (PSVT) in patients with disabling symptoms without structural heart disease
Extended release capsule: Prolong the time to recurrence of symptomatic atrial fibrillation in patients without structural heart disease
Hypersensitivity to propafenone or any component of the formulation; sinoatrial, AV, and intraventricular disorders of impulse generation and/or conduction (except in patients with a functioning artificial pacemaker); Brugada syndrome, sinus bradycardia; cardiogenic shock; uncompensated cardiac failure; marked hypotension; bronchospastic disorders or severe obstructive pulmonary disease; uncorrected electrolyte abnormalities
Canadian labeling: Additional contraindications (not in US labeling): MI within past 3 months; severe hepatic impairment; myasthenia gravis; concurrent use with ritonavir
In the National Heart, Lung, and Blood Institutes Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non " “life-threatening ventricular arrhythmias who had a myocardial infarction (MI) more than 6 days but less than 2 years previously, an increased rate of death or reversed cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide (class IC antiarrhythmics) compared with that seen in patients assigned to placebo (3%). The average duration of treatment with encainide or flecainide in this study was 10 months.
The applicability of the CAST results to other populations (eg, those without recent MI) or other antiarrhythmic drugs is uncertain, but at present, it is prudent to consider any IC antiarrhythmic to have a significant risk in patients with structural heart disease. Given the lack of any evidence that these drugs improve survival, generally avoid antiarrhythmic agents in patients with non " “life-threatening ventricular arrhythmias, even if the patients are experiencing unpleasant, but not life-threatening, symptoms or signs.
Note: Patients who exhibit significant widening of QRS complex or second- or third-degree AV block may need dose reduction.
Atrial fibrillation (to prevent recurrence): Oral:
Extended release capsule: Initial: 225 mg every 12 hours; dosage increase may be made at a minimum of 5-day intervals; may increase to 325 mg every 12 hours; if further increase is necessary, may increase to 425 mg every 12 hours
Immediate release tablet: Initial: 150 mg every 8 hours; dosage increase may be made at minimum of 3- to 4-day intervals, may increase to 225 mg every 8 hours; if further increase is necessary, may increase to 300 mg every 8 hours
Paroxysmal supraventricular tachycardia (to prevent recurrence), ventricular arrhythmias: Oral: Immediate release tablet: Initial: 150 mg every 8 hours (US labeling) or 300 mg every 12 hours (Canadian labeling); dosage increase may be made at minimum of 3- to 4-day intervals, may increase to 225 mg every 8 hours; if further increase is necessary, may increase to 300 mg every 8 hours
Paroxysmal atrial fibrillation, pharmacologic cardioversion (off-label use): Oral: Immediate release tablet: Outpatient: Pill-in-the-pocket" dose: 450 mg (weight <70 kg), 600 mg (weight ≥70 kg). May not repeat in ≤24 hours (Alboni, 2004; AHA/ACC/HRS [January, 2014]). Note: An initial inpatient cardioversion trial should have been successful before sending patient home on this approach. Patient must be taking an AV nodal-blocking agent (eg, beta-blocker, nondihydropyridine calcium channel blocker) prior to initiation of antiarrhythmic.
Refer to adult dosing.
There are no dosage adjustments provided in the manufacturers labeling; however, 50% of propafenone metabolites (some active) are excreted in the urine; some data suggest that no dosage adjustment is necessary (Burgess, 1989; Fromm, 1994); however, use with caution.
Hemodialysis/CVVH: Minimally dialyzable (Burgess, 1989; Seto, 1999); supplemental dose not necessary
US labeling: There are no dosage adjustment provided in the manufacturer 's labeling; however, dosage reduction should be considered as drug undergoes hepatic metabolism. Use with caution.
Canadian labeling:
Mild to moderate impairment: Initial: 150 mg once daily; dosage increase may be made at minimum of 4-day intervals to 150 mg twice daily, then to 150 mg every 8 hours; if further increase is necessary, may increase to 300 mg every 12 hours
Severe impairment: Use is contraindicated.
Oral: Capsules should be swallowed whole; do not crush or chew; may be taken without regard to meals.
The Canadian labeling recommends the tablet be swallowed whole with liquid and to be administered with food.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Extended Release 12 Hour, Oral, as hydrochloride:
Rythmol SR: 225 mg, 325 mg, 425 mg [contains soybean lecithin]
Generic: 225 mg, 325 mg, 425 mg
Tablet, Oral, as hydrochloride:
Rythmol: 150 mg [DSC], 225 mg [scored]
Generic: 150 mg, 225 mg, 300 mg
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Amiodarone: May enhance the adverse/toxic effect of Propafenone. Specifically, the combination may result in altered cardiac conduction and repolarization. Amiodarone may increase the serum concentration of Propafenone. Avoid combination
Antiarrhythmic Agents (Class Ia): Propafenone may enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class Ia). Management: Concurrent use of propafenone with quinidine, amiodarone, or other class IA or class III antiarrhythmics should be avoided. Treatment with such agents should be withheld for at least 5 half-lives prior to initiation of propafenone. Avoid combination
Antiarrhythmic Agents (Class III): Propafenone may enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III). Management: Concurrent use of propafenone with quinidine, amiodarone, or other class IA or class III antiarrhythmics should be avoided. Treatment with such agents should be withheld for at least 5 half-lives prior to initiation of propafenone. Avoid combination
Antihepaciviral Combination Products: May increase the serum concentration of Propafenone. Management: Canadian labeling recommends avoiding this combination. Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Asunaprevir: May increase the serum concentration of Propafenone. Avoid combination
Beta-Blockers: Propafenone may increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Exceptions: Atenolol; Carteolol (Ophthalmic); Levobunolol; Metipranolol; Nadolol. Monitor therapy
Boceprevir: May increase the serum concentration of Propafenone. Monitor therapy
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy
Cardiac Glycosides: Propafenone may increase the serum concentration of Cardiac Glycosides. Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Avoid combination
Cimetidine: May increase the serum concentration of Propafenone. Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Colchicine: P-glycoprotein/ABCB1 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. Consider therapy modification
CYP2D6 Inhibitors (Moderate): Propafenone may increase the serum concentration of CYP2D6 Inhibitors (Moderate). Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Propafenone. Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Propafenone. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Propafenone. Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Etravirine: May decrease the serum concentration of Propafenone. Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
FLUoxetine: Propafenone may enhance the QTc-prolonging effect of FLUoxetine. FLUoxetine may increase the serum concentration of Propafenone. Avoid combination
FluvoxaMINE: May increase the serum concentration of Propafenone. Monitor therapy
Fosamprenavir: May increase the serum concentration of Propafenone. Management: Concurrent use of ritonavir-boosted fosamprenavir with propafenone is contraindicated. The use of non-ritonavir-boosted fosamprenavir with propafenone is not specifically contraindicated but should only be undertaken with caution. Avoid combination
Highest Risk QTc-Prolonging Agents: Moderate Risk QTc-Prolonging Agents may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Ivabradine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy
MiFEPRIStone: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination
Mirabegron: May increase the serum concentration of Propafenone. Management: Monitor clinical response to propafenone closely. Dose adjustment may be necessary. Canadian mirabegron labeling recommends restricting the maximum adult mirabegron dose to 25 mg/day in patients receiving propafenone. Monitor therapy
Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Moderate Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Orlistat: May decrease the serum concentration of Propafenone. Monitor therapy
Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification
PARoxetine: May increase the serum concentration of Propafenone. Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy
Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 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.). Monitor therapy
Propranolol: Propafenone may increase the serum concentration of Propranolol. Monitor therapy
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
QuiNIDine: May enhance the QTc-prolonging effect of Propafenone. QuiNIDine may increase the serum concentration of Propafenone. Avoid combination
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Ritonavir: May increase the serum concentration of Propafenone. Avoid combination
Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy
Saquinavir: May enhance the arrhythmogenic effect of Propafenone. Saquinavir may increase the serum concentration of Propafenone. Avoid combination
Sertraline: May enhance the QTc-prolonging effect of Propafenone. Sertraline may increase the serum concentration of Propafenone. Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Simeprevir: May increase the serum concentration of Propafenone. Monitor therapy
St Johns Wort: May decrease the serum concentration of Propafenone. Monitor therapy
Telaprevir: May enhance the adverse/toxic effect of Propafenone. Monitor therapy
Theophylline Derivatives: Propafenone may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Tipranavir: May increase the serum concentration of Propafenone. Avoid combination
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
Venlafaxine: Propafenone may increase the serum concentration of Venlafaxine. Management: Monitor for increased venlafaxine levels/adverse effects (e.g., hallucinations, agitation, confusion) with propafenone initiation/dose increase. Conversely, monitor for decreased venlafaxine levels with profapenone discontinuation/dose decrease. Monitor therapy
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Vinflunine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination
Vitamin K Antagonists (eg, warfarin): Propafenone may increase the serum concentration of Vitamin K Antagonists. Monitor therapy
ECG, blood pressure, pulse (particularly at initiation of therapy)
1% to 10%:
Cardiovascular: New or worsened arrhythmia (proarrhythmic effect) (2% to 10%), angina (2% to 5%), CHF (1% to 4%), ventricular tachycardia (1% to 3%), palpitation (1% to 3%), AV block (first-degree) (1% to 3%), syncope (1% to 2%), increased QRS interval (1% to 2%), chest pain (1% to 2%), PVCs (1% to 2%), bradycardia (1% to 2%), edema (0% to 1%), bundle branch block (0% to 1%), atrial fibrillation (1%), hypotension (0% to 1%), intraventricular conduction delay (0% to 1%)
Central nervous system: Dizziness (4% to 15%), fatigue (2% to 6%), headache (2% to 5%), ataxia (0% to 2%), insomnia (0% to 2%), anxiety (1% to 2%), drowsiness (1%)
Dermatologic: Rash (1% to 3%)
Gastrointestinal: Nausea/vomiting (2% to 11%), unusual taste (3% to 23%), constipation (2% to 7%), dyspepsia (1% to 3%), diarrhea (1% to 3%), xerostomia (1% to 2%), anorexia (1% to 2%), abdominal pain (1% to 2%), flatulence (0% to 1%)
Neuromuscular & skeletal: Tremor (0% to 1%), arthralgia (0% to 1%), weakness (1% to 2%)
Ocular: Blurred vision (1% to 6%)
Respiratory: Dyspnea (2% to 5%)
Miscellaneous: Diaphoresis (1%)
<1% (Limited to important or life-threatening): Agranulocytosis, alopecia, amnesia, anemia, apnea, AV block (second or third degree), asystole, AV dissociation, cardiac arrest, cholestasis (0.1%), coma, confusion, CHF, depression, granulocytopenia, hepatitis (0.03%), hyperglycemia, impotence, increased bleeding time, leukopenia, lupus erythematosus, mania, memory loss, nephrotic syndrome, paresthesia, peripheral neuropathy, pruritus, psychosis, purpura, renal failure, seizure (0.3%), SIADH, sinus node dysfunction, thrombocytopenia, tinnitus, torsade de pointes, ventricular fibrillation, vertigo
Cl is reduced and elimination half-life is increased.
Concerns related to adverse effects:
- Agranulocytosis: Agranulocytosis has been reported; generally occurring within the first 2 months of therapy. Upon therapy discontinuation, WBC usually normalized by 14 days.
- CNS effects: May cause dizziness, fatigue, blurred vision; caution patients about performing dangerous tasks (eg, driving, operating machinery).
- Conduction disturbances: Slows atrioventricular conduction, potentially leading to first degree AV block; degree of PR interval prolongation and increased QRS duration are dose and concentration related. Avoid in patients with conduction disturbances (unless functioning pacemaker present).
- Hepatotoxicity: Hepatic abnormalities (including fulminant hepatitis and fatalities) have been reported; toxicity appeared due to hepatocellular injury and/or cholestasis.
- Proarrhythmic effects: Can cause life-threatening drug-induced arrhythmias, including ventricular fibrillation, ventricular tachycardia, asystole, and torsade de pointes (Hii, 1991). The manufacturer notes that propafenone may increase the QT interval; however, due to QRS prolongation; changes in the QT interval are difficult to interpret. In an evaluation of propafenone (450 mg/day) in healthy individuals compared to other selected antiarrhythmic agents, propafenone did not affect repolarization time (eg, QT, QTc, JT, JTc) only depolarization time (ie, QRS interval) (Sarubbi, 1998). Monitor for proarrhythmic effects, and when necessary, adjust dose to prevent QTc prolongation.
Disease-related concerns:
- Brugada syndrome: Initiation of propafenone may unmask Brugada syndrome; obtain ECG after treatment initiation and discontinue if ECG indicative of Brugada syndrome.
- Electrolyte imbalance: Use is contraindicated in patients with uncorrected electrolyte abnormalities. Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.
- Heart failure (HF): Avoid use in patients with HF; similar agents have been shown to increase mortality in this population; may precipitate or exacerbate condition (Lindenfeld, 2010).
- Hepatic impairment: Use with caution in patients with hepatic impairment. The Canadian labeling contraindicates use in severe impairment.
- Lupus erythematosus: Positive ANA titers have been reported with use. Titers have decreased with and without therapy discontinuation. Positive titers have not usually been associated with clinical symptoms, although at least one case of drug induced lupus erythematosus has been reported. Consider therapy discontinuation in symptomatic patients with positive ANA titers.
- Myasthenia gravis: Use with caution in patients with myasthenia gravis; may exacerbate condition. The Canadian labeling contraindicates use in patients with myasthenia gravis.
- Pulmonary disease: Propafenone use may be considered in patients with obstructive lung disease who do not have bronchospasm (AHA/ACC/HRS [January, 2014]). Use in patients with bronchospastic disease or severe obstructive lung disease is contraindicated.
- Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- CAST trial: [US Boxed Warning]: In the Cardiac Arrhythmia Suppression Trial (CAST), recent (>6 days but <2 years ago) myocardial infarction patients with asymptomatic, non-life-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. Antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
- Pacemakers: May alter pacing and sensing thresholds of artificial pacemakers.
C
Adverse events were observed in some animal reproduction studies. Propafenone and its metabolite cross the placenta and can be detected in the newborn (Libardoni 1991). Guidelines are available for use during pregnancy (ESG [Regitz-Zagrosek 2011]). Propafenone may be used for the ongoing management of pregnant women with highly symptomatic SVT. The lowest effective dose is recommended; avoid use during the first trimester if possible (Page [ACC/AHA/HRS 2015]).Until more information is available, when treatment of AF or long term treatment of SVT is needed in pregnant women, propafenone is generally reserved for use when other agents are not effective (ESG [Regitz-Zagrosek 2011]).
Propafenone is a class 1c antiarrhythmic agent which possesses local anesthetic properties, blocks the fast inward sodium current, and slows the rate of increase of the action potential. Prolongs conduction and refractoriness in all areas of the myocardium, with a slightly more pronounced effect on intraventricular conduction; it prolongs effective refractory period, reduces spontaneous automaticity and exhibits some beta-blockade activity.
Well absorbed
Vd: Adults: 252 L
Hepatic via CYP2D6, CYP3A4 and CYP1A2 to two active metabolites (5-hydroxypropafenone and N-depropylpropafenone) then ultimately to glucuronide or sulfate conjugates. Two genetically determined metabolism groups exist (extensive and poor metabolizers); 10% of Caucasians are poor metabolizers. Exhibits nonlinear pharmacokinetics; when dose is increased from 300-900 mg/day, serum concentrations increase tenfold; this nonlinearity is thought to be due to saturable first-pass effect.
Urine (<1% unchanged; remainder as glucuronide or sulfate conjugates); feces
Serum: IR: 3.5 hours; ER: 3-8 hours
Extensive metabolizers: 2-10 hours; Poor metabolizers: 10-32 hours
95% to alpha1-acid glycoprotein
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, vomiting, loss of strength and energy, constipation, change in taste, headache, or anxiety. Have patient report immediately to prescriber signs of dehydration, signs of infection, angina, bradycardia, tachycardia, severe dizziness, passing out, arrhythmia, shortness of breath, excessive weight gain, swelling of arms or legs, tremors, change in balance, or blurred vision (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.