A.T.10 (Solution) Instructions for Use

Marketing Authorization Holder

Merck, KGaA (Germany)

ATC Code

A11CC02 (Dihydrotachysterol)

Active Substance

Dihydrotachysterol (Rec.INN registered by WHO)

Dosage Form

A.T.10

Oral solution 1 mg/1 ml: 15 ml bottle with dropper

Dosage Form, Packaging, and Composition

Oral solution transparent, slightly yellowish, oily.

Excipients: medium-chain triglycerides.

15 ml – glass bottles (1) with a dropper cap. – cardboard packs.

Clinical-Pharmacological Group

Drug regulating calcium and phosphorus metabolism

Pharmacotherapeutic Group

Calcium-phosphorus metabolism regulator

Pharmacological Action

Regulator of calcium and phosphorus metabolism. Dihydrotachysterol is similar in chemical structure and mechanism of action to vitamin D₂, is a provitamin D₃, and is equivalent in efficacy to calcitriol (the only difference is in the time of onset of effect).

In hypofunction of the parathyroid glands, it increases plasma calcium concentration by increasing its absorption in the intestine (to a lesser extent than ergocalciferol) and enhancing its transport from bone tissue (in high doses), enhances the mobilization of phosphorus from bone organic compounds and its excretion by the kidneys, reduces ALP activity, stabilizes calcium concentration and binds it in bone tissue, preventing osteoporosis in cases of calcium-phosphorus metabolism disorders. It has weak (compared to ergocalciferol or colecalciferol) antirachitic activity.

It is possible to use for a long time without the development of tolerance.

Pharmacokinetics

Absorption is rapid, in the distal part of the small intestine. In the blood, it binds to alpha-globulins. It is deposited mainly in the liver and adipose tissue.

It is metabolized in the liver to form the active metabolite 25-hydroxydihydrotachysterol. It is excreted in bile and by the kidneys.

Indications

• Hypoparathyroidism (idiopathic and postoperative);
• Pseudohypoparathyroidism.

ICD codes

Dosage Regimen

The daily dose is determined by the doctor individually, depending on the blood calcium level.

Recommended doses for hypoparathyroidism are 0.75-2.5 mg/day for several days, maintenance dose is 0.2-1 mg/day. 0.5 mg of A.T.10 corresponds to approximately 15 drops.

A.T.10 solution can be taken orally on an empty stomach or after meals with a small amount of liquid, or with food (for example, on a piece of bread or sugar); the oily solution does not mix with water. The daily dose of the drug can be taken in several doses.

The duration of treatment is determined by the doctor individually. The patient should be warned that treatment with A.T.10 should not be interrupted independently.

Adverse Reactions

Possible allergic reactions.

Contraindications

• Hypercalcemia;
• Hypervitaminosis D;
• Renal osteodystrophy with hyperphosphatemia;
• Muscle cramps due to hyperventilation
  (hyperventilation tetany);
• Hypersensitivity to vitamin D preparations.

Use with caution in atherosclerosis, pulmonary tuberculosis (in active form), chronic heart failure, hyperphosphatemia, phosphate nephrourolithiasis, in chronic renal failure, sarcoidosis or other granulomatoses, during pregnancy, during lactation (breastfeeding), in elderly patients (may contribute to the development of atherosclerosis), in children.

Use in Pregnancy and Lactation

A.T.10 can be prescribed during pregnancy for vital indications in case of hypocalcemia due to hypoparathyroidism and uncontrolled by calcium preparations alone. In this case, blood calcium concentration should be monitored.

When prescribed in high doses during pregnancy, premature closure of sutures and fontanelles in the fetus may develop.

Dihydrotachysterol crosses the placental barrier in small amounts.

The drug should be used with caution during lactation (breastfeeding), because Dihydrotachysterol is excreted in breast milk in small amounts.

Use in Renal Impairment

Long-term hypercalcemia can lead to nephrotoxic effects, development of urolithiasis, and calcification of the kidneys and tissues.

Pediatric Use

Use the drug with caution in children.

Geriatric Use

Use the drug with caution in elderly patients.

Special Precautions

Treatment should be carried out under the control of blood calcium and phosphorus levels (before treatment, 5-7 days after the start of treatment, and then 1-2 times a month).

The patient is recommended to follow a diet high in calcium and low in phosphorus.

The effect of the drug may persist for up to a month after its discontinuation.

1 mg of dihydrotachysterol is equivalent to 3 mg (120 thousand IU) of ergocalciferol.

Control of laboratory parameters

Since the drug has a narrow therapeutic range, blood concentrations of calcium, phosphates, creatinine, urea nitrogen, and ALP activity should be determined initially once a week, then periodically throughout the entire period of taking the drug in therapeutic doses. The calcium/creatinine index is recommended to be determined every 1-3 months until the patient’s condition stabilizes. Blood calcium concentration should not exceed 8.8-10.3 mg/100 ml. The product of calcium concentration and phosphate concentration (Ca x P) should not exceed 60 mg/dl.

X-ray examination of the skeletal system should be performed every 3 months.

Overdose

Symptoms of hypercalcemia – loss of appetite, nausea, vomiting, diarrhea or constipation, abdominal pain, increased blood pressure, polyuria, thirst, fatigue, muscle weakness, disorientation, drowsiness, pale skin, headache, palpitations. In this case, the drug should be discontinued and blood calcium concentration determined.

Long-term elevation of blood calcium levels can lead to impaired renal function, development of urolithiasis, and calcification of soft tissues and kidneys.

Treatment: if symptoms of hypercalcemia appear, the drug should be discontinued and blood calcium concentration determined. There is no specific antidote for A.T.10 overdose. Treatment of hypercalcemia is carried out by forced diuresis using “loop” diuretics, prescription of a calcium-free diet, corticosteroids, bisphosphonates, and calcitonin. In emergency cases (hypercalcemic crisis) or in patients with renal failure, hemodialysis is performed to reduce serum calcium concentration. After normalization of blood calcium levels, the drug should be resumed and the dose adjusted.

Drug Interactions

Vitamin D, thiazide diuretics, calcium preparations, adrenergic stimulants, and parathyroid hormone enhance hypercalcemia.

When treating with A.T.10 in combination with thyroxine, hypercalcemia may develop after discontinuation of the latter.

Calcium channel blockers, beta-blockers, calcitonin, derivatives of etidronic and pamidronic acids, plicamycin, gallium nitrate, and corticosteroids reduce the effectiveness of A.T.10.

The combination of A.T.10 with fenoterol is not recommended.

In hypervitaminosis, the effect of cardiac glycosides may be enhanced and the risk of arrhythmia may increase due to the development of hypercalcemia (adjustment of the cardiac glycoside dose is advisable).

Under the influence of barbiturates (including phenobarbital), phenytoin, and primidone, the requirement for dihydrotachysterol may increase significantly, which is expressed in increased osteomalacia or severity of rickets (due to accelerated metabolism of dihydrotachysterol with the formation of inactive metabolites due to induction of microsomal enzymes).

Long-term therapy with the drug against the background of simultaneous use of aluminum- and magnesium-containing antacids increases the plasma concentration of dihydrotachysterol and the risk of intoxication (especially in the presence of chronic renal failure).

Cholestyramine, colestipol, and mineral oils reduce the absorption of fat-soluble vitamins from the gastrointestinal tract and require an increase in their dose.

Dihydrotachysterol increases the absorption of phosphorus-containing drugs and the risk of hyperphosphatemia.

Concomitant use with other vitamin D analogs (especially calcifediol) increases the risk of hypervitaminosis (combination is not recommended).

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature from 18°C (64.4°F) to 25°C (77°F).

Shelf Life

Shelf life – 5 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.