CALCITRIOL

(for veterinary information only)

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 mostly used in the treatment of chronic kidney failure though it can also be used in hypocalcemia (low blood calcium). The relationship between calcitriol (active Vitamin D) and parathyroid hormone is somewhat complicated but it is not possible to understand the function of this medication without some understanding of the system.

Calcitriol goes by several names: Active Vitamin D3, 1,25 dihydroxycholecalciferol, & 1,25(OH)2D3. It is probably easiest to just call it "calictriol," the "trio" referring to the 3 hydroxyl groups that define it. The biochemistry of vitamin D is very different from that of other vitamins because vitamin D is actually a hormone. To understand how calcitriol is helpful therapeutically, it is necessary to understand some background information about vitamin D, its metabolic opposite “parathyroid hormone,” and the general calcium and phosphorus balance within the body.

A REVIEW OF VITAMIN D

The story of vitamin D begins when a vitamin D precursor is eaten. The precursor we get from plants is called “ergosterol” and the precursor we get from eating animal tissues is called “cholecalciferol.” These substances are absorbed into the body for eventual activation. (In humans, cholecalciferol can be made anew out of cholesterol with the help of sunlight, hence the term "the sunshine vitamin.") After intestinal absorption both forms of vitamin D go to the liver for processing into their respective forms of "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.

ACTIONS OF VITAMIN D AND PARATHYROID HORMONE

Blood calcium levels are tightly regulated by calcitriol and parathyroid hormone. There are four tiny parathyroid glands around the thyroid gland in the throat area. These glands produce a biochemical called “parathyroid hormone” often abbreviated “PTH.” When blood calcium drops, parathyroid hormone is secreted heavily. PTH performs several actions to help bring the blood calcium level back up:

• PTH mobilizes calcium from bone into the bloodstream.
• PTH instructs the kidney to retain calcium and not excrete it into urine. 

Calcitriol adds in its own effects:

• Calcitriol enhances calcium absorption from food.
• Calcitriol further mobilizes bone calcium. 

Calcitriol shuts off PTH secretion. In this system, calcitriol not only assists in solving the low calcium problem, it also shuts the system down when the problem has been solved. It should be noted that calcitriol is present in one's system all the time, not only when calcium is low. During times of low calcium, though, calcitriol levels are elevated. These hormones work together to maintain the blood calcium level in a very specific range.

WHAT HAPPENS IN KIDNEY FAILURE?

When the kidney is diseased, it becomes unable to remove/excrete phosphorus from the bloodstream and blood phosphorus levels begin to rise. Phosphorus does two bad things at this point: it directly stimulates PTH secretion and it inhibits the enzyme needed to convert calcidiol into calcitriol. This means there is tons of PTH mobilizing calcium from the bones, leaving them soft and easily broken. 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 PTH 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 of the owners and veterinarians of nearly 2000 pets in chronic renal failure has been formulated.  These animals all received calcitriol. Approximately 80% of the owners reported that their pets were brighter and more social and had better appetites on calictriol. It was also felt that these animals had a substantially longer life span than patients not receiving calcitriol.

SIDE EFFECTS

If calcitriol elevates 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

Phosphate binders are common in the treatment of kidney disease. 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 calctriol.

CAUTIONS AND CONCERNS

• Calictriol cannot be used in patients that have an elevated (greater than 6 mg/dl) plasma phosphorus level. Calicitriol 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 at room temperature in the container provided.
• Special compounding pharmacies are needed to create an oral liquid or capsule in a size beneficial to the individual patient.  A commercial vitamin D supplement is not useful (most over the counter formulas include ergocalciferol which the diseased kidney cannot activate and manufactured doses of the prescription product are too high).

Page last updated: 11/9/2019