What to Know About Hectorol (Doxercalciferol)

Hectorol (doxercalciferol) is a man-made vitamin D analog used to treat secondary hyperparathyroidism in adult patients with chronic kidney disease. It works by being metabolized into the active form of vitamin D, which helps regulate parathyroid hormone, calcium, and phosphorus levels within your bloodstream.

Hectorol can be given by mouth as a capsule or intravenously (through your vein) as an injection.

Uses

To understand how Hectorol works, you have to understand what secondary hyperparathyroidism is, and its relationship to chronic kidney disease.

Patients with significant chronic kidney disease (stage 3, 4, or 5) have low blood calcium levels for two main reasons:

• Their kidneys cannot make enough active vitamin D (your body needs active vitamin D to absorb calcium from your gut)
• Their kidneys cannot remove excess phosphorus from the body (the phosphorus then binds to calcium, further lowering blood calcium levels)

In an attempt to increase blood calcium levels, people with chronic kidney disease (especially those on dialysis) may develop secondary hyperparathyroidism.

With secondary hyperparathyroidism, a person's parathyroid glands become large and hyperactive. They basically vigorously produce and release parathyroid hormone (PTH) in order to try and raise blood calcium levels.

The problem with secondary hyperparathyroidism is that PTH levels can become so high that calcium levels can increase dramatically, causing a serious condition called hypercalcemia.

Besides hypercalcemia, secondary hyperparathyroidism may lead to renal osteodystrophy, which is a form of osteoporosis that increases your risk of bone breaks (fractures).

When Hectorol is taken (either as a capsule or through an injection into your vein), the drug is converted into the active form of vitamin D. As a result, calcium levels increase naturally (by being absorbed through your gut). With higher calcium levels, your body stops stimulating your parathyroid glands, and the PTH hormone levels drop.

Before Taking

Before taking a Hectorol injection or capsule, your healthcare provider will want to be certain that your blood calcium level is not above the upper limit of normal. Calcium levels can be easily tested with a blood calcium test. Blood calcium levels are also monitored during treatment.

Warnings, Precautions, and Contraindications

There are several precautions and contraindications to discuss with your healthcare provider before taking Hectorol.

Very high blood calcium levels can occur when being treated with Hectorol (either the capsules or the injection). Severe hypercalcemia is a medical emergency and can lead to abnormal heart rhythms and seizures.

While your practitioner will monitor your calcium levels prior to starting Hectorol and during treatment, it's important to watch out for and inform your healthcare provider if you experience any symptoms of high blood calcium levels, such as:

• Tiredness
• Foggy thinking
• Loss of appetite
• Nausea and/or vomiting
• Constipation
• Increased thirst
• Increased urination and weight loss

The risk of developing hypercalcemia is increased when Hectorol is used with the following drugs:

• High dose calcium preparations
• Thiazide diuretics
• Vitamin D compounds

High calcium levels increase the risk of digitalis toxicity in patients using digitalis drugs, like Digox (digoxin). In addition to monitoring calcium levels, signs, and symptoms of digitalis toxicity will be monitored during treatment with Hectorol.

Serious, even life-threatening allergic reactions (anaphylactic shock) have been reported in patients after the administration of Hectorol.

Allergic reactions may include symptoms, such as:

• Swelling of the face, lips, tongue, and airways
• Chest discomfort
• Trouble breathing

Be sure to tell your healthcare provider if you have had an allergic reaction to Hectorol in the past.

Adynamic bone disease, which is characterized by low bone turnover, may develop in patients on Hectorol. This disease increases the risk of bone fractures if intact PTH levels get too low.

Other Vitamin D Analogues

It's important to mention that besides Hectorol (doxercalciferol), there are five other vitamin D analogs available.

These vitamin D analogs include:

• Rocaltrol (calcitriol)
• Zemplar (paricalcitol)
• One-Alpha (alfacalcidol)—not available in the United States
• Fulstan (falecalcitriol)–not available in the United States
• Maxacalcitol (22-oxacalcitriol)—not available in the United States

Dosage

The dosing regimen for Hectorol depends on whether it is being administered intravenously (injection) or orally (a soft gelatin capsule).

Dosing: Injection

According to the manufacturer, for patients with PTH levels greater than 400 picograms per milliliter (400 pg/mL), Hectorol may be initiated as a 4 microgram (mcg) injection, three times a week, at the end of dialysis.

If the blood parathyroid hormone (PTH) level is not decreased by 50% and the blood parathyroid hormone level remains above 300 pg/mL, the Hectorol dose can be increased by 1 to 2 micrograms per dose at eight-week intervals. The maximum dose is 18 mcg weekly.

Once the blood PTH level has decreased by 50%, even if it remains above 300 pg/ml, or if the blood PTH level is between 150 and 300 mg/mL, the dose is maintained.

If the PTH level falls below 100 pg/mL, the drug will be stopped. Hectorol can be resumed one week later at a dose that is at least 2.5 mcg lower than the previous dose.

Dosing: Capsule

According to the manufacturer, for patients with stage 3 or 4 chronic kidney disease, the Hectorol dose is initiated at 1 mcg orally once daily.

The dose can then be increased by 0.5 mcg at two-week intervals if the PTH level is higher than 70 pg/mL (for stage 3 patients) and higher than 110 pg/mL (for stage 4 patients). The maximum recommended dose of Hectorol capsules is 3.5 mcg once daily.

The dose is maintained if the PTH level is between 35 and 70 pg/ml (for stage 3 patients) and 70 to 110 pg/mL (for stage 4 patients).

Hectorol should be stopped for one week if the PTH level is less than 35 pg/ml (for stage 3 patients) or less than 70 pg/mL (for stage 4 patients). If the drug was stopped, it should be restarted after one week at a dose that is at least 0.5 mcg lower than the previous dose.

For patients on dialysis, oral Hectorol is started as a 10 mcg dose three times a week at dialysis. The maximum weekly dose is 20 mcg three times per week, which is equivalent to 60 mcg weekly.

Monitoring and Modifications

For dialysis patients on Hectorol, calcium, phosphorus, and PTH levels should be checked after starting the drug or after a dose adjustment.

For stage 3 or stage 4 patients on Hectorol capsules, calcium, phosphorus, and PTH levels should be checked at least every two weeks for three months after starting the drug or after a drug adjustment. The levels are then checked every month for three months, and then every three months thereafter.

Patients with liver impairment may not metabolize Hectorol properly, and therefore, will require more frequent monitoring of PTH, calcium, and phosphorus levels.

It's important to tell your healthcare provider if you are pregnant or nursing. Hectorol should not be used during pregnancy (unless clearly needed, according to the manufacturer). Mothers who are breastfeeding should stop the drug (or stop breastfeeding) and watch out for signs and symptoms of hypercalcemia in their baby (if exposed).

Some of the signs and symptoms of hypercalcemia in a baby may include:

• Feeding problems
• Vomiting
• Constipation
• Seizure

Side Effects

The most common side effects in patients with stage 3 or stage 4 chronic kidney disease taking Hectorol include:

• Infection
• Urinary tract infection
• Chest pain
• Constipation
• Indigestion
• Low red and white blood cell count
• Dehydration
• Swelling
• Depression
• Muscle stiffness
• Insomnia
• Lack of energy
• Numbness and tingling
• Increased cough
• Shortness of breath
• Itching
• Sinus pain and inflammation
• Runny nose

The most common side effects in patients with chronic kidney disease on dialysis taking Hectorol include:

• Headache
• Malaise
• Swelling
• Nausea and vomiting
• Shortness of breath
• Dizziness
• Itching
• Low heart rate (called bradycardia)

Interactions

As mentioned above, hypercalcemia may be increased when Hectorol is taken with certain calcium-containing drugs, vitamin D compounds, or thiazide diuretics. Likewise, hypercalcemia can increase the risk of digitalis toxicity for patients taking Digox (digoxin).

Other potential drug interactions include the following:

• The metabolism of Hectorol into active vitamin D may be inhibited by a class of drugs called cytochrome P450 inhibitors (e.g., the antifungal drug ketoconazole and the antibiotic erythromycin). If a patient starts or stops a cytochrome P450 inhibitor, the dosing of Hectorol may need to be adjusted. PTH and calcium levels will also need to be monitored.
• Since Hectorol is activated by an enzyme in the liver called CYP 27, drugs that induce this enzyme, such as glutethimide or phenobarbital, may affect the drug's metabolism. If a CYP 27 inducer is started or stopped, the dosing of Hectorol may need to be adjusted. PTH and calcium levels will also require monitoring.
• Taking high doses of magnesium-containing products (e.g., antacids) with Hectorol may increase blood levels of magnesium. Therefore, patients on dialysis should avoid taking magnesium-containing products if they are also on Hectorol.
• Cholestyramine, mineral oil, and other substances that may affect fat absorption in the gut may impair Hectorol capsule absorption. To avoid this potential interaction, Hectorol capsules should be given at least one hour before or four to six hours after taking such substances.