CRYSTODIGIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CRYSTODIGIN (CRYSTODIGIN).
Cardiac glycoside that inhibits the Na+/K+-ATPase pump, leading to increased intracellular sodium, which in turn promotes calcium influx via the Na+/Ca2+ exchanger, resulting in increased myocardial contractility (positive inotropy). It also has negative chronotropic and dromotropic effects via vagomimetic action.
| Metabolism | Primarily renal excretion; minimal hepatic metabolism. Not significantly metabolized by cytochrome P450 enzymes. |
| Excretion | Primarily renal excretion of unchanged drug; ~80-90% eliminated in urine, ~10-20% in feces via biliary excretion. |
| Half-life | Terminal elimination half-life approximately 1.6–1.9 days (38–45 hours) in patients with normal renal function; prolonged in renal impairment. |
| Protein binding | ~20–25% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd approximately 5–10 L/kg, indicating extensive tissue distribution; clinical significance: large Vd means low plasma concentration relative to total body load, necessitating loading doses. |
| Bioavailability | Oral: 60–80% (variable, depends on formulation and gastrointestinal factors); Intravenous: 100%. |
| Onset of Action | Intravenous: 5–30 minutes; Oral: 0.5–2 hours. |
| Duration of Action | Therapeutic effect persists for 3–4 days after cessation due to slow elimination; clinical monitoring of toxicity signs recommended. |
| Molecular Weight | 780.94 |
0.5 mg intravenously over 2-4 hours, then 0.25 mg every 6 hours as needed up to a total of 1.5 mg in 24 hours.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: reduce dose by 25-50%; CrCl <10 mL/min: reduce dose by 50-75% or use alternative. |
| Liver impairment | Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use. |
| Pediatric use | Loading dose: 10-20 mcg/kg intravenously over 2-4 hours; maintenance: 5-10 mcg/kg every 6 hours as needed. |
| Geriatric use | Start at lower end of dosing range (0.25 mg intravenously), adjust based on renal function and response, monitor for toxicity. |
| 1st trimester | Digitalis glycosides cross the placenta. Available data suggest an association with decreased birth weight and possibly preterm delivery. Use only if clearly needed and benefit outweighs risk. |
| 2nd trimester | Same risks as first trimester. Monitor maternal digoxin levels closely as dosage adjustments may be needed due to changes in volume of distribution and renal function. |
| 3rd trimester | Risk of fetal bradycardia and toxic effects. Monitor fetal heart rate. Use lower doses if necessary. |
Clinical note
Comprehensive clinical and safety monograph for CRYSTODIGIN (CRYSTODIGIN).
| Placental transfer | Crosses placenta; cord blood levels approximate maternal serum levels. |
| Breastfeeding | Digitalis glycosides are excreted into breast milk in low concentrations, but amounts ingested are unlikely to cause adverse effects in infants. However, caution is advised, especially with high maternal doses or impaired infant renal function. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to digitalis glycosidesVentricular fibrillationVentricular tachycardia (unless due to heart failure)Wolff-Parkinson-White syndrome with atrial fibrillationSecond- or third-degree heart block (unless pacemaker present)Obstructive hypertrophic cardiomyopathy
| Precautions | Narrow therapeutic index; toxicity can be life-threatening., Hypokalemia, hypomagnesemia, and hypercalcemia increase risk of digoxin toxicity., Electrolyte monitoring and dose adjustment in renal impairment., Patients with acute myocardial infarction, myocarditis, or severe pulmonary disease may be at increased risk of arrhythmias. |
| Food/Dietary | Avoid high-fiber foods and large amounts of bran or pectin, as they may reduce absorption. Grapefruit juice may increase blood levels; limit consumption. Consistent dietary potassium intake is important; extremes (high or low) can affect drug action. |
Loading safety data…
| Lactation Rating | L2 (Safe) |
| Teratogenic Risk | Pregnancy Category C. First trimester: Association with fetal cardiac glycoside toxicity and malformations in animal studies; limited human data. Second trimester: Potential for fetal bradycardia and hypoxia due to placental transfer. Third trimester: Risk of neonatal digitalis toxicity, including arrhythmias and heart block. |
| Fetal Monitoring | Maternal: Serum digoxin levels, ECG, renal function, electrolytes (K+, Mg2+). Fetal: Heart rate monitoring, ultrasound for hydrops or arrhythmias. Neonatal: ECG and serum digoxin levels at birth. |
| Fertility Effects | No known direct effects on fertility in humans. Animal studies show no impairment at therapeutic doses. |
| Clinical Pearls | Crystodigin (digitoxin) has a very long half-life (~5-7 days) requiring careful monitoring to avoid accumulation. Unlike digoxin, it is primarily hepatically metabolized, so renal impairment has less impact on dosing. Always check for drug interactions with CYP3A4 inducers/inhibitors. Therapeutic monitoring of serum levels is essential (target 15-25 ng/mL). |
| Patient Advice | Take exactly as prescribed; do not miss doses or double up. · Report any symptoms of toxicity: nausea, vomiting, visual disturbances (yellow-green halos), or irregular heartbeat. · Avoid over-the-counter medications without consulting your doctor, especially antacids and laxatives. · Keep regular appointments for blood tests to monitor drug levels and kidney function. · Do not stop suddenly; withdrawal can worsen heart condition. |