Medicine

Calcitriol
Calcium acetate
Calcium Carbonate
Cinacalcet
Sevelamer

Calcitriol (systematic): Drug information

Pharmacologic Category

  •         Vitamin D Analog

 

Dosing: Adult

 

Secondary Hyperparathyroidism in Chronic Kidney disease:

 

For Patients on Dialysis: Oral: Initial dose: 0.25 mcg once a day (manufacturer’s labelling)

Some experts advocate more conservative initial doses (e.g. 0.25 mcg thrice a week). Further, the dosage may be increased by 0.25mcg every other day.

 

IV: Start off carefully: 0.5mcg three times a week is the lowest recommended dose in the manufacturer’s labelling. Some experts approve more conservative initial doses (e.g. 0.25 mcg three times a week). They advocate adjusting the dose by 0.5 to 1 mcg at 2 to 4-week intervals.

 

Dosage range: 0.5 to 4 mcg 3 times a week. When there is a rise in the PTH level in response to therapy, the gradual dose reduction and discontinuation of the therapy may be necessary.

 

Patients with acute, chronic kidney disease not yet on dialysis:

 

Note: The magnitude of the PTH response is highly fluctuating. KDIGO regulation recommends starting with low doses independent of initial PTH concentration and then adjusting based on PTH response while avoiding hypercalcemia.

 

Oral: Initial dose is recommended to 0.25 mcg once a day (manufacturer’s labelling). Some experts recommend more conservative initial doses (e.g. 0.25 mcg 3 to 4 times weekly), and if the need arises, the dosage is increased to 0.5 mcg per day.

 

Discontinuation of therapy for hypercalcemia: It is advocated to discontinue the therapy if hypercalcemia occurs. It is recommended to monitor calcium and phosphorous levels daily until levels normalize. Upon normalization, treatment with calcitriol can be regained at a regular dose than that previously used. Examine your dietary calcium intake and adjust as specified.

 

Administration: Adult

 

IV: This may be allowed as bolus dose IV through the catheter at the end of hemodialysis.

 

Oral: May be administered without considering food. However, it is advisable to help with meals to reduce GI issues.

 

Adverse reactions:

 

The following drug reactions and appearances are derived from product labelling unless otherwise mentioned.

 

>10%: Endocrine & metabolic: Hypercalcemia

 

Contraindications:

Ø  Hypersentivity to calcitriol,

Ø   Other Vitamin D analogues,

Ø   Any component of the formulation hypercalcemia,

Ø   Vitamin D toxicity.

 

 

 

Dietary considerations

 

 Dosage may be taken without considering meals. However, it is advisable to administer the dose with meals to reduce GI concerns. It is essential to maintain sufficient calcium intake during the therapy. There might be a need to limit the consumption of dietary phosphorous.

 

Mechanism of action:

 

  •         Calcitriol, the active form of Vitamin D (1,25 hydroxyvitamin D3), binds to activates Vitamin D receptors in the kidney, parathyroid gland, intestine, and the bone invigorating the intestinal calcium transport and absorption.
  •         It minimizes the parathyroid hormone (PTH)  levels and improves calcium and phosphate homeostasis by restoring the bone resorption of calcium and elevating renal tubular reabsorption of calcium.
  •         Decrease the renal conversion of vitamin D to its primary active metabolite (1,25 hydroxyvitamin D) in chronic renal failures leads to reduced activation of vitamin D receptor, which eventually withdraws restrictive repression of parathyroid hormone (PTH) release.
  •         Increased serum PTH (secondary hyperparathyroidism) minimizes calcium excretion and intensifies bone resorption.

 

Pharmacodynamics and Pharmacokinetics

At the start of action: Oral: 2 hours, maximum effect: 10 hours

 

Duration: Oral, IV: 3 to 5 days

                                                                           Absorption: Oral: Rapid

                                                                        Protein binding: 99.9%

                                                                        Metabolism: Predominantly to calcitroic acid and a lactone metabolite

Renal function impairment: The half-life is increased by at least two-fold 

Calcium acetate: Drug information

Pharmacologic Category

  •         Antidote
  •         Calcium salt
  •         Phosphate Binder

Dosing: Adult

Control of Serum phosphorus: Chronic Kidney Disease:

 Oral: Initially, 1334 mg with each meal is administered. This can be moderately increased (every 2 to 3 weeks) to bring the serum phosphate to the chosen range as long as hypercalcemia does not emerge. Here the usual dosage recommended is 2001 to 2668 mg calcium acetate along with each meal. No additional calcium acetate supplements are to be administered.

Dietary supplement (OTC): 1 to 3 tablets are to be consumed with meal thrice a day

Dosing: Renal Impairment: Adult:

No adjustment of dose is required

Dosing: Hepatic Impairment: Adult:

No adjustment of dose is provided in the manufacturer’s labelling.

Administration: Adult

Oral: The dose is to be taken along with the meals

Adverse reactions:

The following adverse drug responses and appearances are derived from the product labelling unless otherwise mentioned:

≥10%:

Endocrine & metabolic: Hypercalcemia

Gastrointestinal : Diarrhea (oral solution)

Contradictions

Hypercalcemia

Warnings and Precautions

Concerns about unfavorable effects:

  •         Gastrointestinal effects
  •         Hypercalcemia

Dietary considerations

Oral dosage forms must be consumed with meals to be fruitful

Mechanism of Action

It blends with dietary phosphate to form insoluble calcium phosphate, which is discharged in stools.

 

Pharmacodynamics and Pharmacokinetics

  •         Absorption: 30% to 40%
  •         Requires Vitamin D otherwise persistent high doses of calcium acetate are given
  •         Calcium is absorbed in the solution, Ionized form
  •         In an acid environment, solubility of the calcium is increased

Indian brands

  •         Fosbind
  •         Septacal
  •         Phostat

Calcium Carbonate: Drug information

Pharmacologic Category

  •         Antacid
  •         Antidote
  •         Calcium salt
  •         Electrolyte Supplement oral
  •         Phosphate Binder

 

Dosage for Adults for various concerns :

 

Note: 1gm of calcium carbonate is equal to 400mg of elemental calcium.

 

  1.       Antacid – Oral: Normally, it is advised to take 1 to 4 tablets as symptoms occur. Maximum is recommended to take 8 gm per day as calcium carbonate for up to two weeks.

 

Over-the-Counter dosing recommendations may differ by product and/or manufacturer, and specific product labelling should be consulted.

 

  1.       Calcium supplementation (OTC labelling): Orally, it is advised to take 500mg or 4 gm per day as calcium carbonate (equal to 200 mg to 1.6 g of elemental calcium) in 1:3 divided doses.

 

Note: The advocated daily intake of elemental calcium (from the dietary sources and additional sources if required) for optimal health of your bones is 1.2g per day (for women post-menopause) or 1 to 1.2 g per day in other adults.

 

It is desirable to obtain these daily amounts primarily through dietary sources. There is no documentation that the intakes higher than those recommended improve the strength of the bone.

 

  1.       Hyperphosphatemia in Chronic Kidney disease ( off-label usage):

Oral: Total dose of elemental calcium (including dietary sources and calcium-based phosphate binders) should not go beyond 2 gm per day.

 

  1.       Hypoparathyroidism (management of chronic hypocalcemia) (off-label usage):

Oral: 500 mg to 1 g of elemental calcium consumed 2 to 3 times a day. However, the required dose can vary greatly and may be required for more frequent dosing.

 

Note: IV calcium may be administered in acute hypocalcemia with corrected calcium less than 7mg per dL [less than or equal to 1.75mmol per L] or in severely chronic patients, e.g. those patients with arrhythmias, broncho-or laryngospasm, tetany, seizures) 

 

  1.       Concomitant therapy: Significant drug interactions persist, requiring dose per frequency adjustment or avoidance. It is advisable to consult the drug interaction database for any further additional information.

 

  1.       Renal Impairment: Dose for adult: Crcl<25mL per minute: Dosage adjustments may be required based on serum calcium levels.

 

Dosage considerations: 1g calcium carbonate is equal to elemental calcium of 400mg, which is further equivalent to calcium 20mEq which is again comparable to calcium 10mmol

 

Administration Adult: Oral: Administer with food. Doses > 600 mg (elemental calcium) per day should be divided for optimal absorption. One can swallow the whole capsules or have them after opening them and mix the contents with the food or any drink.

 

 

 

Food interactions

 

Food may enhance calcium absorption. Calcium may reduce the absorption of iron. Bran, foods that are high in oxalates or whole-grain cereals may decrease the absorption of calcium.

 

Consideration of the diet: It is advisable to take calcium carbonate with food. Also, it is recommended to limit the intake of bran, foods with high oxalates, or whole-grain cereals that may reduce calcium absorption.

 

Reference range:

 

Calcium supplementation:

 

Serum calcium: 8.5 to 10.5 mg per dL (2.12 to 2.62 mmol/L)

 

Due to the poor interaction between the serum iodized calcium (free) and total serum calcium, especially in low albumin or acid to base imbalances, direct measurement of ionized calcium is advised.

 

In the state of low albumin, the corrected total serum calcium may be evaluated by:

 

Corrected total calcium (mg per dL) = measured serum calcium (mg/mL) + 0.8 (4-measured serum albumin [g/dL])

 

Or

 

Corrected total calcium (mmol per L) = measured serum calcium (mmol/L) +0.02 (40-measured serum albumin [g/L])

 

Hypoparathyroidism – Calcium supplementation –

Correct serum calcium to low- normal range or no more than 0.5mg per dL below normal; calcium-phosphate product less than 55 mg²/dL²

 

Calcium (total): Adults: 9 to 11mg/dL (2.05 to 2.54 mmol/L), may slightly reduce with age. Avoid hypercalcemia for chronic kidney ailment (CKD) stages G3a to G5D

 

Phosphorus: 2.5 to 4.5 mg per dL (0.81 to 1.45 mmol/L). Lower elevated phosphorous levels towards the normal range for CKD stages G3a to G5D.

 

PTH:

 

CKD stage G3a to G5: Here, the optima PTH level is unknown, so it is essential to evaluate the patients with constantly elevated intact PTH levels or if levels are regularly moving above the normal range 

 

Dialysis patients: Maintain intact parathyroid hormone (iPTH) within 2 to 9 times the upper limit of normal.

 

 Some of the  Indian brands:

  1. 4 bone
  2. Shelcal
  3. Cipcal

           

 

 

 

 

 

 

Cinacalcet: Drug information

Pharmacologic Category – Calcimimetic

Dosage for adults:

  1.       Hyperparathyroidism, primary: Oral: Initial dosage: 30 mg daily, afterwards progressively increase the dosage every week 2 to 4 weeks (to 60 mg twice daily, 90mg twice daily, and 90mg 3 or 4 times a day) as required to revitalise the levels of serum calcium.

 

  1.       Hyperparathyroidism, secondary: Oral: Initial: 30mg once daily, afterwards progressively increase the dosage every 2 to 4 weeks (to 60mg once daily, 90 mg once daily, 120 mg once daily, and 180 mg once daily) as required to maintain intact parathyroid hormone (iPTH) level between 150 to 300 pg per mL. It can be used alone or combined with vitamin D and or with phosphate binders.

 

  1.       Conversion from etelcalcetide: It is recommended discontinuing etelcalcetide for a minimum of 4 weeks before starting with cinacalcet. (Not available in India).

 

  1.       Parathyroid carcinoma: Oral dosage: Initially 30mg twice daily is recommended, then it progressively dosage is to be increased every 2 to 4 weeks (to 60 mg twice daily, 90 mg twice daily, and 90mg 3 to 4 times daily) as required to regulate the levels of serum calcium.

 

  1.       Dosage adjustment for concomitant therapy: Significantly drug interactions exist, requiring the adjustment of the frequency of the dose or avoidance thereof. It is advisable to consult the drug interactions database for further added information.

 

  1.       Dosage adjustment for toxicity: Adult

 

  1.       Dosage adjustment for hypocalcemia:

If iPTH is more diminutive than 150pg per mL, then reduce the dose or discontinue cinacalcet and or vitamin D

  1.       Hyperparathyroidism, secondary: If serum calcium is more than 7.5mg per dL but less than 8.4 mg per dL, or if hypocalcemia symptoms occur, then it is recommended to use calcium-containing phosphate binders and or vitamin D to raise the level of calcium

 

If serum calcium is less than 7.5 mg per dL or if hypocalcemia symptoms persist and the dose of vitamin D cannot be increased then, abstain cinacalcet until the serum calcium is greater or equal to 8 mg per dL or symptoms of hypocalcemia resolve, then re-start the cinacalcet at the next lowest dose.

 

Administration: Adult

 

 It is recommended to administer with food or shortly after the meal. Never crush, chew or break the tablet and have it whole.

 

 

 

Adverse reaction:

 

The following unfavourable drug reactions and incidences are deprived of the product labelling unless otherwise mentioned:

 

  •         >10%:
  •         Cardiovascular: Hypotension – 12%

 

  •         Endocrine & Metabolic: Hypocalcemia (< 8.4 mg/dL: 6% to 75%; < 7.5 mg/dL: 29% to 33%), hyporparathyroidism (intact parathyroid hormone (iPTH) < 100 pg/mL: less than equal to 11%)

 

  •         Gastrointestinal: Nausea (29% to 31%), vomiting (26% to 27%), diarrhea (21%), abdominal pain (11%).

 

  •         Nervous system: Headache (12%)              

 

  •         Neuromuscular & skeletal: Muscle spasm (11% to 18%), myalgia (15%), back pain (12%)

 

  •         Respiratory: Dyspnea (13%), cough (12%)

 

Contradictions:

Serum calcium is less than the lower limit of the standard range

Warning and precautions

Concerns about adverse effects:

  •         Adynamic bone disease: This may develop if iPTH levels are repressed less than 100pg per mL. It is recommended to reduce the dosage or discontinue cinacalcet and vitamin D if iPTH levels decrease below 150 pg per mL.
  •         Cardiovascular effects
  •         GI effects
  •         Hypocalcemia: A life-threatening and fatal event about hypocalcemia has happened. Never go for the therapy if the corrected serum calcium is less than the lower limit of normal

Food interactions

Food increases bio-availability.

Management: It is recommended to administer dosage with food or shortly after a meal.

 

 

Reference range: CKD K/DOQI guidelines of stages: 1

  1.       Chronic disease is kidney damage or GFR less than 60 mL per minute per 1.73m² for more or equal to 3 months.
  2.       Stage 2: GFR 60 to 89 mL per minute per 1.73m². This causes damage to the kidney because of a mild decrease in GFR.
  3.       Stage 3: GFR 30 to 59 mL per minute 1.73m². This means a moderate decrease in GFR
  4.       Stage 4: GFR 15 to 29 mL per minute per 1.73m² means a severe decrease in GFR
  5.       Stage 5: GFR less than 15mL per minute per 1.73m² or dialysis. This is a kidney failure

The target range for iPTH: Adults:

Stage 3 CKD: 35 to 70pg per mL

Stage 4 CKD: 70 to 110 pg per mL

Stage 5 CKD: 150 to 300 pg per mL

Serum Phosphorus for adults

Stage 3 and 4 CKD: more significant than equal to 2.7 to less than 4.6 mg per dL

Stage 5: CKD: 3.5 to 5.5 mg per dL               

Serum calcium-phosphorus product: Adults:

Stage 3 to 5 CKD: less than 55mg²/dL²

Process of action:

The drug increases the calcium-sensing receptor on the parathyroid gland, simultaneously lowering parathyroid hormone, serum calcium, and serum phosphorous levels, thereby preventing the growing bone disease and adverse events related to mineral metabolism disorders.

Indian brands

  1.       Capicet
  2.       SENACEPT
  3.       Pth
  4.       SETZ

 

Sevelamer: Drug information

Pharmacologic Category: Phosphate Binder

Dosing: Adult

Note: The dosage of both sevelamer carbonate and sevelamer hydrochloride is the same. So when switching from one product to another, the same dose measured on an mg/mg basis should be applied.

Control of serum phosphorous: Oral

  1. For those patients who are not consuming a phosphate binder initially, it is recommended dosage of 800 to 1,600 mg to be administered a day thrice with meals, and the initial dose may be based on serum phosphorous levels, which will be within the given below range:

>5.5 mg/dL to <7.5 mg/dL: 800 mg 3 times a day

≥7.5 mg/dL to <9 mg/dL: 1,200 to 1,600 mg 3 times a day

≥9mg/dL: 1,600 mg 3 times a day

  1. Maintenance dose adjustment based on serum phosphorous concentration – the goal range was and as under and based on the range the dose was administered:
  •         3.5 to 5.5 mg/dL: maximum dose studied was equal to 13g/day of sevelamer hydrochloride or 14 g/day of sevelamer carbonate
  •         >5.5 mg/dL: Increase by 400 to 800 mg per meal at 2-week intervals
  •         3.5 to 5.5 mg/dL: Maintain the current dose
  •         <3.5 mg/dL: Decrease by 400 to 800 mg/meal

 

Dosage adjustment when switching between phosphate binder products: 667 mg of calcium acetate is equal to ~800 mg sevelamer (carbonate or hydrochloride)

 

  1. Conversion based on dosage per meal:

        

  1.       Calcium acetate 667 mg: Convert to 800 mg
  2.       Calcium acetate 1,334 mg: Convert to 1,600 mg 2) or 1,200 mg
  3.       Calcium acetate 2001 mg: Convert to 2,400 mg or 2000 mg

 

Dosing: Renal impairment: Adult

 

There are no dosage adjustments in the manufacturer’s labelling, and the matter has not been studied yet.

 

Dosing: Hepatic Impairment: Adult

There is no dosage adjustment provided in the manufacturer’s labelling.

 

Administration: Audit

 

It is recommended to take medicine with meals. It should be consumed immediately or within 30 minutes. If you dissolve the pill in water, the oral suspension needs to be re-suspended immediately before drinking.

 

Tablets: It should be swallowed whole without crushing, chewing, or breaking.

 

 

 

Adverse reactions:

 

The following adverse drug reactions and incidences are derived from product labelling unless otherwise specified:

 

  •         >10%:

 

  •         Endocrine & metabolic: Metabolic acidosis (For children: 34% [Pieper 2006]; adults: Frequency not defined)
  •         Gastrointestinal: Diarrhea (19%), dyspepsia (16%), nausea (20%), vomiting (22%)

 

 

Allergic symptoms

 

Hyper-sensitivity to sevelamer or any component of the formulation: bowel obstruction

 

 

 

Indian brands:

 

  1.       Zynagel
  2.       Biosev
  3.       Foseal
  4.       Acutrol
  5.       Revlamer

6.        Sevcar