Also called 1,25 dihydroxycholecalciferol

Brand Name: Rocaltrol

Usually compounded to the size to fit an individual patient (the 0.25 microgram capsules are far too big for animals under 200 lbs)       

Background

Calcitriol is another name for active vitamin D. Vitamin D is crucial to the regulation of blood and bone calcium levels, blood phosphorus levels, and parathyroid hormone levels. You may be familiar with vitamin D as the "sunshine vitamin" or you may take Vitamin D capsules yourself, but calcitriol is different. The vitamin D you consume orally is not active and must undergo several well-regulated steps to be converted into calcitriol. It is used to prevent progression in chronic kidney failure, as well as to raise blood calcium levels in some forms of hypocalcemia. Vitamin D is actually a hormone rather than a vitamin in the usual sense.

A Review of Vitamin D

Contains ergosterol (pre-vitamin D2) (original graphic courtesy Marvistavet.com)

Calcitriol goes by several names: Active vitamin D3; 1,25 dihydroxycholecalciferol; and 1,25(OH) 2D3. It is probably easiest to just call it calcitriol. The word calcitriol contains the root "trio," meaning three. This refers to the three hydroxyl groups that define it. The vitamin D molecule must have all three of these hydroxyls before it can be considered active. Let's review how the vitamin D you eat becomes calcitriol.

The story of vitamin D begins when a vitamin D precursor is eaten. The precursor we get from plants is called ergosterol, which eventually becomes vitamin D2. The precursor we get from eating animal tissues is called cholecalciferol, which eventually becomes vitamin D3. (In humans, cholecalciferol can be made anew out of cholesterol with the help of sunlight, hence the term "the sunshine vitamin." Dogs and cats do not make pre-vitamin D in this way.)  If you take a vitamin D supplement yourself, look at the label. Chances are it will say "Vitamin D3 as cholecalciferol."

Contains cholecalciferol (pre-vitamin D3) original graphic Cortesy of Marvistavet

After oral consumption and intestinal absorption of a plant or animal vitamin D precursor, both forms of vitamin D go to the liver to be processed into calcidiol; a second hydroxyl group is added, hence the "di" (meaning two) in the name. Calcidiol is not yet fully activated until it goes to the kidney for final processing (addition of the third hydroxyl group) to make calcitriol, the full-fledged hormone ready to go to work in calcium regulation. The calcitriol that is most active in our bodies and the one that we use as a medication is the D3 (animal origin) form, rather than the D2 plant form.

Actions of Vitamin D (Calcitriol) and Parathyroid Hormone

Calcitriol and parathyroid hormone work together to raise blood calcium. They do this by mobilizing calcium from bone, enhancing intestinal absorption of calcium from consumed food, and reducing calcium loss in urine. Parathyroid hormone enhances activation of vitamin D into calcitriol and when there is enough calcitriol, parathyroid hormone production shuts down so that both hormone levels drop together after blood calcium levels have been restored.  In short, both hormones raise blood calcium. Parathyroid hormone promotes calcitriol production but calcitriol shuts off parathyroid hormone production.  The balance in these two hormones allows for blood calcium levels to be tightly regulated.

What Happens in Kidney Failure?

In early kidney failure, the kidney is not able to activate vitamin D efficiently nor is it able to adequately excrete phosphorus. As a result active vitamin D levels drop (which results in a drop in blood calcium) and blood phosphate levels start to climb.  The calcium drop is seen by the parathyroid gland, parathyroid hormone is released, and hopefully the situation can be normalized.

When the kidney is diseased, it becomes unable to remove/excrete phosphorus from the bloodstream so blood phosphorus levels begin to rise. Phosphorus does two bad things at this point: it directly stimulates parathyroid hormone secretion and it inhibits the enzyme needed to convert calcidiol into calcitriol. This means there is tons of parathyroid hormone mobilizing calcium from the bones, leaving them soft and easily broken, and inadequate calcitriol to shut the system down. The calcium mobilized from the bone promptly combines with the extra phosphorus in the blood to form calcium phosphate crystals all over the body. These crystals are inflammatory and interfere with normal body functions. Calcitriol is not produced in amounts adequate to shut off the extra parathyroid hormone and the system is out of control.

How this Medication is Used

By giving active vitamin D in pill or liquid form, the above disaster can hopefully be averted or reversed. (It is more easily averted than reversed.) It has been established that parathyroid hormone is an important toxin in kidney failure and we want to reduce its secretion. This is best done with minute (measured in units 1000 times smaller than the usual dosages) quantities of vitamin D. These quantities are enough to shut off parathyroid hormone secretion but are not high enough to lead to elevated phosphorus levels.

If calcitriol is started early in kidney failure, parathyroid levels may be kept low enough that calcium/phosphorus imbalance never becomes an issue. If it is started later in failure, it is helpful but may not be able to provide as good a response.

Recently a survey was taken of the owners and veterinarians of nearly 2,000 pets in chronic renal failure.  The animals all received calcitriol. Approximately 80 percent of the owners reported that their pets were brighter and more social and had better appetites on calcitriol. It was also felt that these animals had a substantially longer life span than patients not receiving calcitriol.

Side Effects

If calcitriol raises serum calcium levels, this can lead to calcium precipitation in the kidneys, making kidney damage worse. Calcitriol cannot be given to patients with elevated serum calcium levels and monitoring is necessary to make sure serum calcium levels do not rise. Similarly, calcitriol cannot be given to patients where phosphorus is too high.

It is important to watch for signs of high calcium: excessive thirst and urination, appetite loss.

It is also important to watch for signs of low calcium: twitching, tremors, and even seizures.

Interactions with other Drugs

If the binder in use contains calcium elevated blood, calcium levels could become a concern. If calcitriol is used with a magnesium containing phosphate binder, magnesium levels can get too high.

Concurrent use with phenobarbital for seizure control can reduce the effect of calcitriol.

Concurrent use with corticosteroids can greatly reduced the effectiveness of calcitriol

Corticosteroids, such as prednisolone, may negate the desired effects of calcitriol. If possible, these medications should not be combined.

Cautions and Concerns

• Calcitriol cannot be used in patients that have an elevated (greater than 6 mg/dl) plasma phosphorus level. Calcitriol might elevate phosphorus further at this stage, which is exactly what we do not want. In such patients, plasma phosphorus must be reduced by diet, fluid administration, or by phosphate binders before calcitriol can be started.
  
  
• It is helpful to monitor parathyroid hormone levels in patients on calcitriol therapy as some dosage adjustment is sometimes beneficial depending on the parathyroid hormone level. This kind of monitoring is not crucial to calcitriol use, however.

• Calcitriol can be given with or without food but is best given on an empty stomach. If a dose is skipped, do not double up on the next dose but pick up with the next scheduled dose.

• Store the commercial product at room temperature, away from light. Store any compounded product in accordance with the pharmacy's instructions.

• Compounding pharmacies may be needed to create an oral liquid or capsule in a size beneficial to the individual patient. A commercial vitamin D supplement is not useful as most over the counter formulas include ergocalciferol that the diseased kidney cannot activate, and manufactured doses of the prescription product are too high. When using a compounding pharmacy, it is important to ensure they know how to keep the Calcitriol active and not oxidized in a liquid. When possible, manufactured Calcitriol can be used instead of compounded. It is available in a 250 ng or 500 ng capsule and a liquid (1000 ng/ml).