Triamcinolone Acetonide (BAN, JAN) is known as Triamcinolone in the US.
International Drug Name Search
Glossary
| BAN | British Approved Name |
| JAN | Japanese Accepted Name |
Generic Name: droperidol (dro PER i dol)
Brand Names: Inapsine
Droperidol is a sedative, tranquilizer, and anti-nausea medication.
Droperidol is used to reduce nausea and vomiting caused by surgery or other medical procedures.
Droperidol may also be used for purposes other than those listed in this medication guide.
Before you receive droperidol, tell your doctor if you have heart disease, high blood pressure, a heart rhythm disorder, low potassium, liver or kidney disease, adrenal gland cancer, or a history of alcohol abuse.
Before you receive droperidol, tell your doctor if you have been taking any medications to treat high blood pressure, a heart rhythm disorder, malaria, infections, a prostate disorder, depression or mental illness, or if you are using a narcotic pain medication.
Before you receive droperidol, tell your doctor if you are allergic to any drugs, or if you have:
heart disease;
heart rhythm disorder;
congestive heart failure;
high blood pressure;
an electrolyte imbalance (such as low potassium);
liver or kidney disease;
adrenal gland cancer (pheochromocytoma); or
a history of alcohol abuse.
If you have any of these conditions, you may not be able to receive droperidol, or you may need a dose adjustment.
Droperidol is given as an injection through a needle placed into a muscle or a vein. You will receive this injection in a clinic or hospital setting prior to and/or during your surgery or medical procedure.
Since droperidol is given as needed by a healthcare professional, it is not likely that you will miss a dose.
Overdose symptoms may include fast or pounding heartbeats, dizziness, uneven heart rate, or fluttering in your chest.
feeling like you might pass out;
dizziness, fainting, fast or pounding heartbeat, fluttering in your chest;
chest tightness and trouble breathing;
fever, stiff muscles, confusion, sweating, fast or uneven heartbeats;
confusion, hallucinations;
tremor (uncontrolled shaking); or
restless muscle movements in your eyes, tongue, jaw, or neck.
Less serious side effects include:
drowsiness, dizziness; or
feeling restless or anxious.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
Usual Adult Dose for Nausea/Vomiting:
To reduce the incidence of nausea and vomiting associated with surgical and diagnostic procedures:
Dosage: The dosage should be individualized. Factors to be considered in determining dose are age, body weight, physical status, underlying pathological condition, use of other drugs, the type of anesthesia to be used, and the surgical procedure involved. Vital signs and ECG should be monitored closely.
Maximum Dosage: The maximum recommended initial dose is 2.5 mg IM or slow IV. Additional 1.25 mg doses of droperidol may be administered to achieve the desired effect. The additional doses should be administered with caution and only if the potential benefit outweighs the potential risk.
Usual Adult Dose for Nausea/Vomiting -- Postoperative:
To reduce the incidence of nausea and vomiting associated with surgical and diagnostic procedures:
Dosage: The dosage should be individualized. Factors to be considered in determining dose are age, body weight, physical status, underlying pathological condition, use of other drugs, the type of anesthesia to be used, and the surgical procedure involved. Vital signs and ECG should be monitored closely.
Maximum Dosage: The maximum recommended initial dose is 2.5 mg IM or slow IV. Additional 1.25 mg doses of droperidol may be administered to achieve the desired effect. The additional doses should be administered with caution and only if the potential benefit outweighs the potential risk.
Usual Pediatric Dose for Nausea/Vomiting:
To reduce the incidence of nausea and vomiting associated with surgical and diagnostic procedures:
Dosage: The dosage should be individualized. Factors to be considered in determining dose are age, body weight, physical status, underlying pathological condition, use of other drugs, the type of anesthesia to be used, and the surgical procedure involved. Vital signs and ECG should be monitored closely.
Children 2 to 12 years:
Postoperative nausea and vomiting (PONV):
Prophylaxis, if high risk for PONV: 0.01 to 0.015 mg/kg/dose IM or IV given near the end of surgery Maximum dose: 1.25 mg
Administer additional doses after at least 6 hours with caution and only if potential benefit outweighs risks.
(Previous reports suggested a higher dose of 0.075 mg/kg as effective; however, due to side effects associated with the higher doses, doses greater than 0.05 mg/kg are considered excessive and no longer recommended.)
Treatment (not first line): IV:
Manufacturer recommendations: 0.1 mg/kg/dose. Administer additional doses with extreme caution and only if potential benefit outweighs risks.
Alternate dosing: Doses as low as 0.01 to 0.015 mg/kg/dose (up to 0.03 mg/kg) may be effective for breakthrough nausea and vomiting
Maximum initial dose: 0.1 mg/kg
Administer additional doses after at least 6 hours with caution and only if potential benefit outweighs risks.
Usual Pediatric Dose for Nausea/Vomiting -- Postoperative:
To reduce the incidence of nausea and vomiting associated with surgical and diagnostic procedures:
Dosage: The dosage should be individualized. Factors to be considered in determining dose are age, body weight, physical status, underlying pathological condition, use of other drugs, the type of anesthesia to be used, and the surgical procedure involved. Vital signs and ECG should be monitored closely.
Children 2 to 12 years:
Postoperative nausea and vomiting (PONV):
Prophylaxis, if high risk for PONV: 0.01 to 0.015 mg/kg/dose IM or IV given near the end of surgery Maximum dose: 1.25 mg
Administer additional doses after at least 6 hours with caution and only if potential benefit outweighs risks.
(Previous reports suggested a higher dose of 0.075 mg/kg as effective; however, due to side effects associated with the higher doses, doses greater than 0.05 mg/kg are considered excessive and no longer recommended.)
Treatment (not first line): IV:
Manufacturer recommendations: 0.1 mg/kg/dose. Administer additional doses with extreme caution and only if potential benefit outweighs risks.
Alternate dosing: Doses as low as 0.01 to 0.015 mg/kg/dose (up to 0.03 mg/kg) may be effective for breakthrough nausea and vomiting
Maximum initial dose: 0.1 mg/kg
Administer additional doses after at least 6 hours with caution and only if potential benefit outweighs risks.
The following drugs can interact with droperidol. Tell your doctor if you are using any of these:
arsenic trioxide (Trisenox);
a diuretic (water pill);
a laxative;
a drug to treat a psychiatric disorder;
an anti-malaria medication;
heart or blood pressure medications (Cartia XT, Procardia, Covera, Isoptin, Verelan and others);
heart rhythm medication such as amiodarone (Cordarone, Pacerone), disopyramide (Norpace), quinidine (Cardioquin, Quinaglute), sotalol (Betapace), and others;
drugs to treat high blood pressure or a prostate disorder, such as doxazosin (Cardura), or prazosin (Minipress);
an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate);
a narcotic pain medication such as hydrocodone (Lortab, Vicodin), morphine (MS Contin), oxycodone (OxyContin, Percocet), propoxyphene (Darvocet, Darvon), and others; or
an antibiotic such as azithromycin (Zithromax), clarithromycin (Biaxin), erythromycin (E-Mycin, E.E.S., Erythrocin, Ery-Tab), and others.
This list is not complete and there may be other drugs that can interact with droperidol. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.
See also: droperidol side effects (in more detail)
Generic Name: phendimetrazine (Oral route)
fen-dye-MET-ra-zeen TAR-trate
In the U.S.
Available Dosage Forms:
Therapeutic Class: Appetite Suppressant, Centrally Acting
Chemical Class: Phendimetrazine
Phendimetrazine is used as part of a short-term plan, along with a low calorie diet, for weight reduction. It is used in obese patients who have not been able to lose weight with diet and exercise alone. Phendimetrazine belongs to the group of medicines known as appetite suppressants.
This medicine is available only with your doctor's prescription.
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Appropriate studies have not been performed on the relationship of age to the effects of phendimetrazine tablets in the pediatric population. Safety and efficacy have not been established.
Use of phendimetrazine slow-release capsules is not recommended in children younger than 12 years of age.
No information is available on the relationship of age to the effects of phendimetrazine in geriatric patients.
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
This section provides information on the proper use of a number of products that contain phendimetrazine. It may not be specific to Bontril. Please read with care.
Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much is taken, it may become habit-forming (causing mental or physical dependence).
This medicine is available in two forms: slow-release capsules and tablets. Ask your doctor which dosage form is right for you.
Carefully follow your doctor's instructions for a reduced-calorie diet plan and regular exercise. Talk with your doctor before starting any exercise program.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and does not cause any unwanted effects.
Do not use phendimetrazine if you are also using similar medicines such as benzphetamine, diethylpropion, mazindol, phentermine, Didrex®, or Suprenza™. Also, do not use this medicine if you have used an MAO inhibitor (MAOI) such as Eldepryl®, Marplan®, Nardil®, or Parnate® within the past 14 days. Using these medicines together may cause serious unwanted effects.
Make sure your doctor knows if you are pregnant or planning to become pregnant before using this medicine.
This medicine may be habit-forming. If you think this medicine is not working properly after you have taken it for a few weeks, do not increase the dose. Instead, check with your doctor.
Stop using this medicine and check with your doctor right away if you notice a decrease in your ability to exercise, if you faint, or if you have chest pain, swelling of your feet or lower legs, or trouble with breathing. These may be symptoms of a very serious heart or lung problem.
This medicine may cause some people to become dizzy, lightheaded, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.
For diabetic patients: This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests or if you have any questions, check with your doctor.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription and nonprescription (over-the-counter) medicines, dietary supplements, herbal remedies, or medicines for appetite control, asthma, colds, cough, hay fever, and sinus problems.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
Get emergency help immediately if any of the following symptoms of overdose occur:
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
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Digoxin Tablets, USP are one of the cardiac (or digitalis) glycosides, a closely related group of drugs having in common specific effects on the myocardium. These drugs are found in a number of plants. Digoxin is extracted from the leaves of Digitalis lanata. The term “digitalis” is used to designate the whole group of glycosides. The glycosides are composed of two portions: a sugar and a cardenolide (hence “glycosides”).
Digoxin is described chemically as (3β,5β,12β) - 3 - [(O - 2,6 - dideoxy - β - D - ribo - hexopyranosyl - (1→4) - O - 2,6 - dideoxy - β - D - ribo - hexopyranosyl - (1→4) - 2,6 - dideoxy - β - D - ribo - hexopyranosyl)oxy] - 12,14 - dihydroxy - card - 20(22) - enolide. lts molecular formula is C41H64O14, its molecular weight is 780.95, and its structural formula is:
Digoxin exists as odorless white crystals that melt with decomposition above 230°C. The drug is practically insoluble in water and in ether; slightly soluble in diluted (50%) alcohol and in chloroform; and freely soluble in pyridine.
Digoxin Tablets, USP are supplied as 125 mcg (0.125 mg) or 250 mcg (0.25 mg) tablets for oral administration. Each tablet contains the labeled amount of digoxin USP and the following inactive ingredients:
125 mcg (0.125 mg): anhydrous lactose, colloidal silicon dioxide, corn starch, D&C yellow #10 aluminum lake, FD&C yellow #6 aluminum lake, lactose monohydrate, magnesium stearate and starch 1500.
250 mcg (0.25 mg): anhydrous lactose, colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate and starch 1500.
Digoxin inhibits sodium-potassium ATPase, an enzyme that regulates the quantity of sodium and potassium inside cells. Inhibition of the enzyme leads to an increase in the intracellular concentration of sodium and thus (by stimulation of sodium-calcium exchange) an increase in the intracellular concentration of calcium. The beneficial effects of digoxin result from direct actions on cardiac muscle, as well as indirect actions on the cardiovascular system mediated by effects on the autonomic nervous system. The autonomic effects include: (1) a vagomimetic action, which is responsible for the effects of digoxin on the sinoatrial and atrioventricular (AV) nodes; and (2) baroreceptor sensitization, which results in increased afferent inhibitory activity and reduced activity of the sympathetic nervous system and renin-angiotensin system for any given increment in mean arterial pressure. The pharmacologic consequences of these direct and indirect effects are: (1) an increase in the force and velocity of myocardial systolic contraction (positive inotropic action); (2) a decrease in the degree of activation of the sympathetic nervous system and renin-angiotensin system (neurohormonal deactivating effect); and (3) slowing of the heart rate and decreased conduction velocity through the AV node (vagomimetic effect). The effects of digoxin in heart failure are mediated by its positive inotropic and neurohormonal deactivating effects, whereas the effects of the drug in atrial arrhythmias are related to its vagomimetic actions. In high doses, digoxin increases sympathetic outflow from the central nervous system (CNS). This increase in sympathetic activity may be an important factor in digitalis toxicity.
Absorption: Following oral administration, peak serum concentrations of digoxin occur at 1 to 3 hours. Absorption of digoxin from Digoxin Tablets has been demonstrated to be 60% to 80% complete compared to an identical intravenous dose of digoxin (absolute bioavailability). When Digoxin Tablets are taken after meals, the rate of absorption is slowed, but the total amount of digoxin absorbed is usually unchanged. When taken with meals high in bran fiber, however, the amount absorbed from an oral dose may be reduced. Comparisons of the systemic availability and equivalent doses for oral preparations of Digoxin Tablets are shown in Table 1.
* For example, 125 mcg Digoxin Tablets equivalent to 100 mcg Digoxin Injection / IV. | |||||
| Product | Absolute | Equivalent Doses (mcg)* | |||
| Bioavailability | Among Dosage Forms | ||||
| Digoxin Tablets | 60 - 80% | 62.5 | 125 | 250 | 500 |
| Digoxin Injection/IV | 100% | 50 | 100 | 200 | 400 |
In some patients, orally administered digoxin is converted to inactive reduction products (e.g., dihydrodigoxin) by colonic bacteria in the gut. Data suggest that one in ten patients treated with Digoxin Tablets will degrade 40% or more of the ingested dose. As a result, certain antibiotics may increase the absorption of digoxin in such patients. Although inactivation of these bacteria by antibiotics is rapid, the serum digoxin concentration will rise at a rate consistent with the elimination half-life of digoxin. The magnitude of rise in serum digoxin concentration relates to the extent of bacterial inactivation, and may be as much as two-fold in some cases.
Following drug administration, a 6- to 8-hour tissue distribution phase is observed. This is followed by a much more gradual decline in the serum concentration of the drug, which is dependent on the elimination of digoxin from the body. The peak height and slope of the early portion (absorption/distribution phases) of the serum concentration-time curve are dependent upon the route of administration and the absorption characteristics of the formulation. Clinical evidence indicates that the early high serum concentrations do not reflect the concentration of digoxin at its site of action, but that with chronic use, the steady-state post-distribution serum concentrations are in equilibrium with tissue concentrations and correlate with pharmacologic effects. In individual patients, these post-distribution serum concentrations may be useful in evaluating therapeutic and toxic effects (see DOSAGE AND ADMINISTRATION: Serum Digoxin Concentrations).
Digoxin is concentrated in tissues and therefore has a large apparent volume of distribution. Digoxin crosses both the blood-brain barrier and the placenta. At delivery, the serum digoxin concentration in the newborn is similar to the serum concentration in the mother. Approximately 25% of digoxin in the plasma is bound to protein. Serum digoxin concentrations are not significantly altered by large changes in fat tissue weight, so that its distribution space correlates best with lean (i.e., ideal) body weight, not total body weight.
Only a small percentage (16%) of a dose of digoxin is metabolized. The end metabolites, which include 3β-digoxigenin, 3-keto-digoxigenin, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation. The metabolism of digoxin is not dependent upon the cytochrome P-450 system, and digoxin is not known to induce or inhibit the cytochrome P-450 system.
Elimination of digoxin follows first-order kinetics (that is, the quantity of digoxin eliminated at any time is proportional to the total body content). Following intravenous administration to healthy volunteers, 50% to 70% of a digoxin dose is excreted unchanged in the urine. Renal excretion of digoxin is proportional to glomerular filtration rate and is largely independent of urine flow. In healthy volunteers with normal renal function, digoxin has a half-life of 1.5 to 2.0 days. The half-life in anuric patients is prolonged to 3.5 to 5 days. Digoxin is not effectively removed from the body by dialysis, exchange transfusion, or during cardiopulmonary bypass because most of the drug is bound to tissue and does not circulate in the blood.
Race differences in digoxin pharmacokinetics have not been formally studied. Because digoxin is primarily eliminated as unchanged drug via the kidney and because there are no important differences in creatinine clearance among races, pharmacokinetic differences due to race are not expected.
The clearance of digoxin can be primarily correlated with renal function as indicated by creatinine clearance. The Cockcroft and Gault formula for estimation of creatinine clearance includes age, body weight, and gender. Table 5 that provides the usual daily maintenance dose requirements of Digoxin Tablets based on creatinine clearance (per 70 kg) is presented in the DOSAGE AND ADMINISTRATION section.
Plasma digoxin concentration profiles in patients with acute hepatitis generally fell within the range of profiles in a group of healthy subjects.
The times to onset of pharmacologic effect and to peak effect of preparations of Digoxin Tablets are shown in Table 2.
* Documented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes. | ||
† Depending upon rate of infusion. | ||
| Product | Time to | Time to |
| Onset of Effect* | Peak Effect* | |
| Digoxin Tablets | 0.5 - 2 hours | 2 - 6 hours |
| Digoxin Injection/IV | 5-30 minutes† | 1 - 4 hours |
Digoxin produces hemodynamic improvement in patients with heart failure. Short- and long-term therapy with the drug increases cardiac output and lowers pulmonary artery pressure, pulmonary capillary wedge pressure, and systemic vascular resistance. These hemodynamic effects are accompanied by an increase in the left ventricular ejection fraction and a decrease in end-systolic and end-diastolic dimensions.
Two 12-week, double-blind placebo-controlled studies enrolled 178 (RADIANCE trial) and 88 (PROVED trial) patients with NYHA class II or III heart failure previously treated with digoxin, a diuretic, and an ACE inhibitor (RADIANCE only) and randomized them to placebo or treatment with Digoxin Tablets. Both trials demonstrated better preservation of exercise capacity in patients randomized to Digoxin Tablets. Continued treatment with Digoxin Tablets reduced the risk of developing worsening heart failure, as evidenced by heart failure-related hospitalizations and emergency care and the need for concomitant heart failure therapy. The larger study also showed treatment-related benefits in NYHA class and patients' global assessment. In the smaller trial, these trended in favor of a treatment benefit.
The Digitalis Investigation Group (DIG) main trial was a multicenter, randomized, double-blind, placebo-controlled mortality study of 6801 patients with heart failure and left ventricular ejection fraction ≤0.45. At randomization, 67% were NYHA class I or II, 71% had heart failure of ischemic etiology, 44% had been receiving digoxin, and most were receiving concomitant ACE inhibitor (94%) and diuretic (82%). Patients were randomized to placebo or Digoxin Tablets, the dose of which was adjusted for the patient's age, sex, lean body weight, and serum creatinine (see DOSAGE AND ADMINISTRATION), and followed for up to 58 months (median 37 months). The median daily dose prescribed was 0.25 mg. Overall all-cause mortality was 35% with no difference between groups (95% confidence limits for relative risk of 0.91 to 1.07). Digoxin was associated with a 25% reduction in the number of hospitalizations for heart failure, a 28% reduction in the risk of a patient having at least one hospitalization for heart failure, and a 6.5% reduction in total hospitalizations (for any cause).
Use of Digoxin Tablets was associated with a trend to increase in time to all-cause death or hospitalization. The trend was evident in subgroups of patients with mild heart failure as well as more severe disease, as shown in Table 3. Although the effect on all-cause death or hospitalization was not statistically significant, much of the apparent benefit derived from effects on mortality and hospitalization attributed to heart failure.
* Number of patients with an event during the first 2 years per 1000 randomized patients. | ||||
† Relative-risk (95% confidence interval). | ||||
‡ DIG Ancillary Study. | ||||
| Risk of All-Cause Mortality or | ||||
| All-Cause Hospitalization* | ||||
| n | Placebo | Digoxin Tablets | Relative risk† | |
| All patients | 0.94 | |||
| (EF ≤0.45) | 6801 | 604 | 593 | (0.88-1.00) |
| 0.96 | ||||
| NYHA I/II | 4571 | 549 | 541 | (0.89-1.04) |
| 0.99 | ||||
| EF 0.25-0.45 | 4543 | 568 | 571 | (0.91-1.07) |
| 0.98 | ||||
| CTR ≤0.55 | 4455 | 561 | 563 | (0.91-1.06) |
| 0.88 | ||||
| NYHA III/IV | 2224 | 719 | 696 | (0.80-0.97) |
| 0.84 | ||||
| EF <0.25 | 2258 | 677 | 637 | (0.76-0.93) |
| 0.85 | ||||
| CTR >0.55 | 2346 | 687 | 650 | (0.77-0.94) |
| 1.04 | ||||
| EF >0.45‡ | 987 | 571 | 585 | (0.88-1.23) |
| Risk of HF-Related Mortality or | ||||
| HF-Related Hospitalization* | ||||
| n | Placebo | Digoxin Tablets | Relative risk† | |
| All patients | 0.69 | |||
| (EF ≤0.45) | 6801 | 294 | 217 | (0.63-0.76) |
| 0.70 | ||||
| NYHA I/II | 4571 | 242 | 178 | (0.62-0.80) |
| 0.74 | ||||
| EF 0.25-0.45 | 4543 | 244 | 190 | (0.66-0.84) |
| 0.71 | ||||
| CTR ≤0.55 | 4455 | 239 | 180 | (0.63-0.81) |
| 0.65 | ||||
| NYHA III/IV | 2224 | 402 | 295 | (0.57-0.75) |
| 0.61 | ||||
| EF <0.25 | 2258 | 394 | 270 | (0.53-0.71) |
| 0.65 | ||||
| CTR >0.55 | 2346 | 398 | 287 | (0.57-0.75) |
| 0.72 | ||||
| EF >0.45‡ | 987 | 179 | 136 | (0.53-0.99) |
In situations where there is no statistically significant benefit of treatment evident from a trial's primary endpoint, results pertaining to a secondary endpoint should be interpreted cautiously.
In patients with chronic atrial fibrillation, digoxin slows rapid ventricular response rate in a linear dose-response fashion from 0.25 to 0.75 mg/day: Digoxin should not be used for the treatment of mufti-focal atrial tachycardia.
Digoxin Tablets are indicated for the treatment of mild to moderate heart failure. Digoxin Tablets increase left ventricular ejection fraction and improve heart failure symptoms as evidenced by exercise capacity and heart failure-related hospitalizations and emergency care, while having no effect on mortality. Where possible, Digoxin Tablets should be used with a diuretic and an angiotensin-converting enzyme inhibitor, but an optimal order for starting these three drugs cannot be specified.
Digoxin Tablets are indicated for the control of ventricular response rate in patients with chronic atrial fibrillation.
Digitalis glycosides are contraindicated in patients with ventricular fibrillation or in patients with a known hypersensitivity to digoxin. A hypersensitivity reaction to other digitalis preparations usually constitutes a contraindication to digoxin.
Because digoxin slows sinoatrial and AV conduction, the drug commonly prolongs the PR interval. The drug may cause severe sinus bradycardia or sinoatrial block in patients with preexisting sinus node disease and may cause advanced or complete heart block in patients with preexisting incomplete AV block. In such patients consideration should be given to the insertion of a pacemaker before treatment with digoxin.
After intravenous digoxin therapy, some patients with paroxysmal atrial fibrillation or flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, leading to a very rapid ventricular response or ventricular fibrillation. Unless conduction down the accessory pathway has been blocked (either pharmacologically or by surgery), digoxin should not be used in such patients. The treatment of paroxysmal supraventricular tachycardia in such patients is usually direct-current cardioversion.
Patients with certain disorders involving heart failure associated with preserved left ventricular ejection fraction may be particularly susceptible to toxicity of the drug. Such disorders include restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, and acute cor pulmonale. Patients with idiopathic hypertrophic subaortic stenosis may have worsening of the outflow obstruction due to the inotropic effects of digoxin. Digoxin should generally be avoided in these patients, although it has been used for ventricular rate control in the subgroup of patients with atrial fibrillation.
Digoxin is primarily excreted by the kidneys; therefore, patients with impaired renal function require smaller than usual maintenance doses of digoxin (see DOSAGE AND ADMINISTRATION). Because of the prolonged elimination half-life, a longer period of time is required to achieve an initial or new steady-state serum concentration in patients with renal impairment than in patients with normal renal function. If appropriate care is not taken to reduce the dose of digoxin, such patients are at high risk for toxicity, and toxic effects will last longer in such patients than in patients with normal renal function.
In patients with hypokalemia or hypomagnesemia, toxicity may occur despite serum digoxin concentrations below 2 ng/mL, because potassium or magnesium depletion sensitizes the myocardium to digoxin. Therefore, it is desirable to maintain normal serum potassium and magnesium concentrations in patients being treated with digoxin. Deficiencies of these electrolytes may result from malnutrition, diarrhea, or prolonged vomiting, as well as the use of the following drugs or procedures: diuretics, amphotericin B, corticosteroids, antacids, dialysis, and mechanical suction of gastrointestinal secretions.
Hypercalcemia from any cause predisposes the patient to digitalis toxicity. Calcium, particularly when administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. On the other hand, hypocalcemia can nullity the effects of digoxin in humans; thus, digoxin may be ineffective until serum calcium is restored to normal. These interactions are related to the fact that digoxin affects contractility and excitability of the heart in a manner similar to that of calcium.
Hypothyroidism may reduce the requirements for digoxin. Heart failure and/or atrial arrhythmias resulting from hypermetabolic or hyperdynamic states (e.g., hyperthyroidism, hypoxia or arteriovenous shunt) are best, treated by addressing the underlying condition. Atrial arrhythmias associated with hypermetabolic states are particularly resistant to digoxin treatment. Care must be taken to avoid toxicity if digoxin is used.
Digoxin should be used with caution in patients with acute myocardial infarction. The use of inotropic drugs in some patients in this setting may result in undesirable increases in myocardial oxygen demand and ischemia.
It may be desirable to reduce the dose of digoxin for 1 to 2 days prior to electrical cardioversion of atrial fibrillation to avoid the induction of ventricular arrhythmias, but physicians must consider the consequences of increasing the ventricular response if digoxin is withdrawn. If digitalis toxicity is suspected, elective cardioversion should be delayed. If it is not prudent to delay cardioversion, the lowest possible energy level should be selected to avoid provoking ventricular arrhythmias.
Digoxin can rarely precipitate vasoconstriction and therefore should be avoided in patients with myocarditis.
Patients with beriberi heart disease may fail to respond adequately to digoxin if the underlying thiamine deficiency is not treated concomitantly.
Patients receiving digoxin should have their serum electrolytes and renal function (serum creatinine concentrations) assessed periodically; the frequency of assessments will depend on the clinical setting. For discussion of serum digoxin concentrations; see DOSAGE AND ADMINISTRATION section.
Potassium-depleting diuretics are a major contributing factor to digitalis toxicity. Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum digoxin concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result. Erythromycin and clarithromycin (and possibly other macrolide antibiotics) and tetracycline may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis intoxication may result (see CLINICAL PHARMACOLOGY: Absorption). Propantheline and diphenoxylate, by decreasing gut motility, may increase digoxin absorption. Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine; certain anticancer drugs, and metoclopramide may interfere with intestinal digoxin absorption, resulting in unexpectedly low serum concentrations. Rifampin may decrease serum digoxin concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of digoxin. There have been inconsistent reports regarding the effects of other drugs [e.g., quinine, penicillamine] on serum digoxin concentration. Thyroid administration to a digitalized, hypothyroid patient may increase the dose requirement of digoxin. Concomitant use of digoxin and sympathomimetics increases the risk of cardiac arrhythmias. Succinylcholine may cause a sudden extrusion of potassium from muscle cells, and may thereby cause arrhythmias in digitalized patients. Although calcium channel blockers and digoxin may be useful in combination to control atrial fibrillation, their additive effects on AV node conduction can result in advanced or complete heart block. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. Digoxin concentrations are increased by about 15% when digoxin and cervedilol are administered concomitantly. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing carvedilol.
Due to the considerable variability of these interactions; the dosage of digoxin should be individualized when patients receive these medications concurrently. Furthermore, caution should be exercised when combining digoxin with any drug that may cause a significant deterioration in renal function, since a decline in glomerular filtration or tubular secretion may impair the excretion of digoxin.
The use of therapeutic doses of digoxin may cause prolongation of the PR interval and depression of the ST segment on the electrocardiogram. Digoxin may produce false positive ST-T changes on the electrocardiogram during exercise testing. These electrophysiologic effects reflect an expected effect of the drug and are not indicative of toxicity.
Digoxin showed no genotoxic potential in vitro studies (Ames test and mouse lymphoma). No data are available on the carcinogenic potential of digoxin, nor have studies been conducted to assess its potential to affect fertility.
Animal reproduction studies have not been conducted with Digoxin. It is also not known whether digoxin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Digoxin should be given to a pregnant woman only if clearly needed.
Studies have shown that digoxin concentrations in the mother's serum and milk are similar. However, the estimated exposure of a nursing infant to digoxin via breastfeeding will be far below the usual infant maintenance dose. Therefore, this amount should have no pharmacologic effect upon the infant. Nevertheless, caution should be exercised when digoxin is administered to a nursing woman.
Newborn infants display considerable variability in their tolerance to digoxin. Premature and immature infants are particularly sensitive to the effects of digoxin, and the dosage of the drug must not only be reduced but must be individualized according to their degree of maturity. Digitalis glycosides can cause poisoning in children due to accidental ingestion.
The majority of clinical experience gained with digoxin has been in the elderly population. This experience has not identified differences in response or adverse effects between the elderly and younger patients. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, which should be based on renal function, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION).
In general, the adverse reactions of digoxin are dose-dependent and occur at doses higher than those needed to achieve a therapeutic effect. Hence, adverse reactions are less common when digoxin is used within the recommended dose range or therapeutic serum concentration range and when there is careful attention to concurrent medications and conditions.
Because some patients may be particularly susceptible to side effects with digoxin, the dosage of the drug should always be selected carefully and adjusted as the clinical condition of the patient warrants. In the past, when high doses of digoxin were used and little attention was paid to clinical status or concurrent medications, adverse reactions to digoxin were more frequent and severe. Cardiac adverse reactions accounted for about one-half, gastrointestinal disturbances for about one-fourth, and CNS and other toxicity for about one-fourth of these adverse reactions. However, available evidence suggests that the incidence and severity of digoxin toxicity has decreased substantially in recent years. In recent controlled clinical trials, in patients with predominantly mild to moderate heart failure, the incidence of adverse experiences was comparable in patients taking digoxin and in those taking placebo. In a large mortality trial, the incidence of hospitalization for suspected digoxin toxicity was 2% in patients taking Digoxin Tablets compared to 0.9% in patients taking placebo. In this trial, the most common manifestations of digoxin toxicity included gastrointestinal and cardiac disturbances; CNS manifestations were less common.
Therapeutic doses of digoxin may cause heart block in patients with pre-existing sinoatrial or AV conduction disorders; heart block can be avoided by adjusting the dose of digoxin. Prophylactic use of a cardiac pacemaker may be considered if the risk of heart block is considered unacceptable. High doses of digoxin may produce a variety of rhythm disturbances, such as first-degree, second-degree (Wenckebach), or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation. Digoxin produces PR prolongation and ST segment depression which should not by themselves be considered digoxin toxicity. Cardiac toxicity can also occur at therapeutic doses in patients who have conditions which may alter their sensitivity to digoxin (see WARNINGS and PRECAUTIONS).
Digoxin may cause anorexia, nausea, vomiting, and diarrhea. Rarely, the use of digoxin has been associated with abdominal pain, intestinal ischemia, and hemorrhagic necrosis of the intestines.
Digoxin can produce visual disturbances (blurred or yellow vision), headache, weakness, dizziness, apathy, confusion, and mental disturbances (such as anxiety, depression, delirium; and hallucination).
Gynecomastia has been occasionally observed following the prolonged use of digoxin. Thrombocytopenia and maculopapular rash and other skin reactions have been rarely observed.
Table 4 summarizes the incidence of those adverse experiences listed above for patients treated with Digoxin Tablets or placebo from two randomized, double-blind, placebo-controlled withdrawal trials. Patients in these trials were also receiving diuretics with or without angiotensin-converting enzyme inhibitors. These patients had been stable on digoxin, and were randomized to digoxin or placebo. The results shown in Table 4 reflect the experience in patients following dosage titration with the use of serum digoxin concentrations and careful follow-up. These adverse experiences are consistent with results from a large, placebo-controlled mortality trial (DIG trial) wherein over half the patients were not receiving digoxin prior to enrollment.
| Adverse Experience | Digoxin Patients | Placebo Patients |
| (n=123) | (n=125) | |
| Cardiac | ||
| Palpitation | 1 | 4 |
| Ventricular extrasystole | 1 | 1 |
| Tachycardia | 2 | 1 |
| Heart arrest | 1 | 1 |
| Gastrointestinal | ||
| Anorexia | 1 | 4 |
| Nausea | 4 | 2 |
| Vomiting | 2 | 1 |
| Diarrhea | 4 | 1 |
| Abdominal pain | 0 | 6 |
| CNS | ||
| Headache | 4 | 4 |
| Dizziness | 6 | 5 |
| Mental disturbances |