Digoxin

Digoxin is a cardiac glycoside, extracted from the leaves of the Digitalis lanata plant. It blocks an enzyme in heart muscle cells called the sodium pump (Na-K ATPase). This raises calcium inside the cells, so the heart squeezes harder with each beat. Digoxin also slows conduction through the AV node, both directly and by stimulating the parasympathetic nervous system, which is how it slows the heart rate in atrial fibrillation.

Digoxin is used to:

• treat mild to moderate heart failure in adults, usually alongside a diuretic and an ACE inhibitor
• control the resting heart rate in adults with chronic atrial fibrillation
• increase the strength of heart muscle contraction in children with heart failure.

In heart failure, digoxin improves symptoms and exercise capacity and reduces hospital admissions, but it does not help people live longer. In atrial fibrillation it slows the resting heart rate but does not restore a normal rhythm, and it does not control heart rate well during exercise. It is not used for multifocal atrial tachycardia.

Digoxin first gained FDA approval on November 16, 1954. It is available as a generic and under the brand name Lanoxin.

Take digoxin exactly as prescribed and read all medication guides.

• Take it at the same time every day
• Measure the oral solution with the calibrated dropper or syringe provided, not a kitchen spoon. If your dose is less than 0.2 mL, ask your pharmacist for a different measuring syringe, as the provided dropper cannot measure doses that small accurately.
• Keep taking digoxin even if you feel well, and refill your prescription before you run out
• Meals high in bran fibre can reduce how much digoxin you absorb, so keep your routine consistent
• Monitor and record your heart rate and blood pressure daily
• Expect regular blood tests to check your digoxin level, kidney function, and electrolytes

Digoxin injection is given into a vein, or occasionally into a muscle, by a healthcare provider when you cannot take it by mouth or a rapid effect is needed. Oral digoxin starts working in 30 minutes to 2 hours, with the strongest effect at 2 to 6 hours. When injected into a vein, it starts working within 5 to 30 minutes.

Digoxin has a narrow therapeutic range. The dose that helps and the dose that causes harm are close together, so your dose is worked out from your weight, age, and kidney function, and you may need blood tests to check your digoxin level. Do not change your dose yourself.

Do not use digoxin if you are allergic to it or to any other digitalis medicine, or if you have ventricular fibrillation.

Tell your doctor before starting if you have Wolff-Parkinson-White syndrome, sick sinus syndrome or AV block without a pacemaker, a recent heart attack, myocarditis, amyloid heart disease, or heart failure with a preserved ejection fraction. Digoxin may be unsuitable or need extra care in each of these.

Your potassium, magnesium, and calcium levels matter. Low potassium or magnesium, or high calcium, makes digoxin toxicity more likely, while low calcium can stop digoxin working. Tell your doctor if you take a diuretic (water tablet) or have been unwell with vomiting or diarrhea, as these can shift these levels quickly.

Impaired kidney function, advanced age, and low body weight all raise the risk of toxicity. Thyroid problems change how you respond to digoxin: an underactive thyroid reduces the dose you need, while arrhythmias linked to an overactive thyroid respond poorly to digoxin. Your kidney function and heart rhythm will be checked regularly.

Do not stop taking digoxin suddenly, as your condition may get worse.

To make sure digoxin is safe for you, tell your doctor if you have ever had:

• sick sinus syndrome or AV block, unless you have a pacemaker
• Wolff-Parkinson-White syndrome
• slow heartbeats that made you faint
• a recent heart attack, myocarditis, or amyloid heart disease
• kidney disease
• an electrolyte imbalance, such as low potassium or magnesium, or high or low calcium
• a thyroid disorder
• recent vomiting or diarrhea, or a condition that affects how well you absorb food

Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant. Decades of experience with digoxin in pregnancy have not shown an increased risk of birth defects or miscarriage. Untreated heart failure or atrial fibrillation in pregnancy carries real risks to both mother and baby, including preterm birth, low birth weight, and death. Digoxin crosses the placenta, so newborns are monitored for signs of toxicity. Your digoxin dose may need to go up during pregnancy and down afterwards, so your levels will be checked.

Breastfeeding

The amount of digoxin a breastfed baby receives is up to about 4% of the dose used to treat a newborn, which is unlikely to be clinically significant. Discuss breastfeeding with your doctor.

Use in children

Digoxin is used in children with heart failure to increase the strength of heart muscle contraction, although its safety and effectiveness in treating heart failure in children have not been established in adequate, well-controlled studies. Its safety and effectiveness for controlling heart rate in children with atrial fibrillation have not been established either. Newborns vary widely in how they tolerate digoxin, and premature babies are particularly sensitive, so doses are individualised. The oral solution is used for infants, young children and anyone with a very low body weight.

Get emergency medical help if you have signs of an allergic reaction to digoxin: an unexplained rash; difficulty breathing; swelling of your mouth, lips or throat.

Signs of digoxin toxicity

Too much digoxin can be dangerous, and the early signs are easy to miss because they overlap with heart failure symptoms. Call your doctor at once if you have:

• nausea, vomiting, loss of appetite, or persistent diarrhea, often the first signs
• blurred vision, or objects looking yellow or green, or halos around lights
• a fast, slow or uneven heartbeat, or a light-headed feeling as though you might pass out
• confusion, weakness, unusual tiredness, hallucinations, or changes in thinking or behaviour

Visual and neurological symptoms can linger after other signs of toxicity have settled. In babies and children, toxicity may show as an abnormal heart rhythm, failure to thrive, weight loss, stomach pain, drowsiness or behaviour changes rather than nausea.

Also, call your doctor at once if you have

• bloody or black, tarry stools, or severe stomach pain
• breast swelling or tenderness
• a rash, or unusual bruising or bleeding.

Serious side effects may be more likely in older adults and in people who are ill or frail.

Common digoxin side effects

The most common side effects of digoxin are:

• nausea, vomiting, diarrhea
• dizziness or feeling weak
• headache, apathy, anxiety or depression
• abdominal pain.

Rash, other skin reactions, and low platelet counts have been reported only rarely.

Side effects are largely dose-related and are less common when your digoxin level stays in the target range. Overall, 5 to 20% of people report an adverse reaction, and about 15 to 20% of those reactions are serious.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Digoxin dosing is individualised. It is based on lean body weight, age, kidney function and any interacting medicines, and it is adjusted according to your response, your digoxin blood level and any signs of toxicity.

Adult digoxin dose for heart failure and atrial fibrillation

Treatment can start with a loading dose if a rapid effect is needed, or with a maintenance dose alone if it is not.

Oral loading dose (if used): 10 to 15 mcg/kg in adults and children over 10 years. Half the total is given first, then a quarter of the total every 6 to 8 hours for two further doses, with clinical review before each one.

Oral maintenance dose: a starting dose of 3.4 to 5.1 mcg/kg per day, given once daily, in adults and children over 10 years with normal kidney function. In practice, this usually works out at 62.5 to 500 mcg once daily depending on lean body weight and creatinine clearance. Doses may be increased every 2 weeks according to response, digoxin levels and tolerability.

Pediatric digoxin dose

• Children 5 to 10 years: oral loading dose 20 to 45 mcg/kg if needed; maintenance 3.2 to 6.4 mcg/kg per dose, twice daily.
• Infants and children under 5 years are dosed by weight using the oral solution, and premature babies need lower, individualised doses.

Digoxin blood levels

Levels below 0.5 ng/mL are associated with reduced benefit, and levels above 2 ng/mL with increased toxicity and no extra benefit. Blood samples are taken just before the next dose, or at least 6 hours after the last one.

Take it as soon as you can, but skip the missed dose if your next dose is due in less than 12 hours. Do not take two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. A digoxin overdose can be fatal. Symptoms include nausea, vomiting, loss of appetite and tiredness, followed by confusion, visual changes and dangerous heart rhythms. Digoxin is not effectively removed by dialysis, but an antidote called digoxin immune Fab (DigiFab) reverses serious toxicity in 80 to 90% of cases.

Avoid becoming overheated or dehydrated during exercise, in hot weather, or by not drinking enough fluids, since dehydration can affect your kidney function and your electrolyte levels, both of which influence how much digoxin builds up in your body. Check with your doctor or pharmacist before starting any new medicine, supplement, or herbal product.

Digoxin interacts with a very large number of medicines, and even a modest change in your digoxin level can matter. Tell your doctor and pharmacist about everything you take, including over-the-counter medicines, vitamins and herbal products. Not all possible interactions are listed here.

Medicines that may raise your digoxin level include:

• Amiodarone, dronedarone, quinidine, propafenone, and ranolazine
• Verapamil, diltiazem, nifedipine, and carvedilol
• Clarithromycin, erythromycin, tetracycline, gentamicin, trimethoprim, and itraconazole
• Ritonavir, saquinavir, and telaprevir
• Spironolactone, captopril, telmisartan, tolvaptan, and conivaptan
• Atorvastatin, ticagrelor, mirabegron, quinine, lapatinib, and nefazodone
• NSAIDs such as ibuprofen and indomethacin, and other medicines that reduce kidney function.

Medicines that may lower your digoxin level include:

• Antacids, sucralfate, cholestyramine, colestipol, and kaolin-pectin
• Rifampin, phenytoin, neomycin, sulfasalazine, and metoclopramide
• St. John's wort, acarbose, miglitol, and exenatide

Medicines that may affect your heart rhythm when taken with digoxin:

• Beta blockers and calcium channel blockers, which can exacerbate a slow heartbeat
• Ivabradine, dofetilide, and sotalol
• Intravenous calcium, succinylcholine, and adrenaline-like medicines such as epinephrine and dopamine
• Thyroid medicines, which may increase how much digoxin you need

Some herbal products, including Siberian ginseng, Asian ginseng, ashwagandha, and Chan Su, can interfere with digoxin blood tests and give a falsely high or low result.

Tablets: store in a dry place at 20°C to 25°C (68°F to 77°F) and protect from light. Keep in a tight, light-resistant container with a child-resistant closure. Do not store in a bathroom.

Oral solution: store at 20°C to 25°C (68°F to 77°F) and protect from light.

Keep digoxin and all medicines out of the reach of children. Do not flush unused medicine. Ask your pharmacist about a take-back programme.