Paricalcitol

Oral Administration

May take with or without food

IV Administration

Administer as an IV bolus no more frequently than every other day at any time during dialysis

Storage

IV

• Store at room temperature of 25°C (77°F); excursions permitted between15-30°C (59-86°F)

Paricalcitol may be found in some form under the following brand names:

• Zemplar

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of vitamin D can cause serious or life-threatening side effects.

Overdose symptoms may include headache, weakness, drowsiness, dry mouth, nausea, vomiting, constipation, muscle or bone pain, metallic taste in the mouth, weight loss, itchy skin, changes in heart rate, loss of interest in sex, confusion, unusual thoughts or behavior, feeling unusually hot, severe pain in your upper stomach spreading to your back, or fainting.

Do not take other vitamin or mineral supplements (including mineral oil), unless your doctor has told you to.

If you also take mineral oil or cholestyramine: Avoid taking either of these medicines within 1 hour after or 4 to 6 hours before you take paricalcitol.

Grapefruit and grapefruit juice may interact with paricalcitol and lead to unwanted side effects. Avoid the use of grapefruit products while taking paricalcitol.

Avoid using calcium supplements or antacids without your doctor's advice. Use only the specific type of supplement or antacid your doctor recommends.

Usual Adult Dose for Secondary Hyperparathyroidism:

Injectable:
Initial dose: 0.04 to 0.1 mcg/kg (2.8 to 7 mcg), injected as a bolus dose through a hemodialysis vascular access port at any time during dialysis

Maximum frequency: Every other day

Comments:
-Do not inject directly into a vein.

Use: Prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease Stage 5.
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Oral:
Initial dose:
Stage 3 or 4 Chronic Kidney Disease (CKD):
Initial dosing is based on baseline intact parathyroid hormone (iPTH):
-500 pg/mL or less: 1 mcg orally daily OR 2 mcg orally 3 times a week
-Over 500 pg/mL: 2 mcg orally daily OR 4 mcg orally 3 times a week

Stage 5 CKD:
Starting dose (micrograms) = baseline iPTH level (pg/mL)/80
Starting dose is given orally 3 times a week; only start if baseline serum calcium has been adjusted to 9.5 mg/dL or lower.

Comments:
-If giving 3 times a week, do not give more often than every other day.

Use: Prevention and treatment of secondary hyperparathyroidism associated with:
-Chronic Kidney Disease (CKD) stages 3 and 4 (oral product only), or
-CKD stage 5 on hemodialysis or peritoneal dialysis (oral or injectable).

Usual Pediatric Dose for Secondary Hyperparathyroidism:

Safety and efficacy have not been established in pediatric patients.
The following is dosing used in a very small pediatric trial.
No data are available on children under 5 years old.

Initial dose, children 5 to 18 years:
0.04 mcg/kg three times per week if baseline intact parathyroid hormone (iPTH) is less than 500 pg/mL
0.08 mcg/kg three times per week if baseline iPTH is 500 pg/mL or higher
-Injected as a bolus dose through a hemodialysis vascular access port at any time during dialysis

Maximum frequency: Every other day

Comments:
-Do not inject directly into a vein.

Use: Prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease Stage 5.

Secondary Hyperparathyroidism

IV paricalcitol used for prevention and treatment of secondary hyperparathyroidism associated with stage 5 chronic kidney disease (CKD).110

Oral paricalcitol used for prevention and treatment of secondary hyperparathyroidism associated with stage 3 and 4 CKD. 117

Paricalcitol is used to treat and prevent hyperparathyroidism in patients with chronic kidney disease who are on dialysis. Hyperparathyroidism is a condition that is caused when the parathyroid glands located in the neck make too much parathyroid hormone (PTH). This hormone controls the concentrations of calcium and phosphorus in your blood. Paricalcitol helps lower the amount of PTH which lowers the calcium and phosphorus concentrations.

paricalcitol is available only with your doctor's prescription.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Blurred vision
• cough or hoarseness
• difficulty with swallowing
• dizziness
• fever or chills
• headache
• hives
• itching
• lower back or side pain
• nervousness
• pain
• painful or difficult urination
• pounding in the ears
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• shortness of breath
• skin rash
• slow or fast heartbeat
• swelling
• tightness in the chest
• unusual tiredness or weakness

• Abdominal or stomach pain
• abnormal growth filled with fluid or semisolid material
• ammonia-like breath odor
• anxiety
• bladder pain
• bloating or swelling of the face, arms, hands, lower legs, or feet
• bloody or cloudy urine
• burning, tingling, numbness or pain in the hands, arms, feet, or legs
• chest pain or discomfort
• cold sweats
• coma
• confusion
• convulsions
• cool, pale skin
• decreased urine
• depression
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• dry mouth
• fainting
• frequent urge to urinate
• general feeling of discomfort or illness
• increase in heart rate
• increased hunger
• increased thirst
• irregular heartbeat
• joint pain
• lightheadedness
• loss of appetite
• muscle aches and pains
• nausea or vomiting
• nightmares
• numbness or tingling in the hands, feet, or lips
• pain or discomfort in the arms, jaw, back, or neck
• rapid breathing
• rapid weight gain
• runny nose
• sensation of pins and needles
• shakiness
• shivering
• slurred speech
• sneezing
• sore throat
• stabbing pain
• sunken eyes
• sweating
• thirst
• trouble sleeping
• troubled breathing
• unusual weight gain or loss
• weight loss
• wrinkled skin

• Large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• slow or irregular breathing

Get emergency help immediately if any of the following symptoms of overdose occur:

• Abdominal or stomach cramps
• constipation
• depression
• high urine levels of calcium
• incoherent speech
• increased urination
• metallic taste
• muscle cramps in the hands, arms, feet, legs, or face
• muscle weakness
• tremor

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• back pain
• belching
• bloody nose
• bruising
• change in vision
• cough producing mucus
• difficulty with moving
• feeling of constant movement of self or surroundings
• heartburn
• impaired vision
• indigestion
• lack or loss of strength
• large, flat, blue, or purplish patches in the skin
• leg cramps
• muscle pain or stiffness
• pain or tenderness around the eyes and cheekbones
• pain, swelling, or redness in the joints
• sensation of spinning
• sores on the skin
• stomach discomfort, upset, or pain
• stuffy nose

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

As reported in adults, unless otherwise noted.

>10%:

Gastrointestinal: Nausea (children, adolescents, and adults: 5% to 13%), diarrhea (7% to 12%)

Infection: Infection (bacterial, fungal, viral: 3% to 15%)

Respiratory: Rhinitis (children and adolescents: 17%)

1% to 10%:

Cardiovascular: Hypertension (7%), edema (6% to 7%), hypotension (5%), palpitations (3%), chest pain (3%), peripheral edema (3%), syncope (3%), atrial flutter (<2%), cardiac arrhythmia (<2%), cerebrovascular accident (<2%), chest discomfort (<2%), ischemic bowel disease (<2%)

Central nervous system: Dizziness (5% to 7%), chills (5%), insomnia (5%), vertigo (5%), headache (3% to 5%), anxiety (3%), depression (3%), fatigue (3%), malaise (3%), abnormal gait (<2%), agitation (<2%), confusion (<2%), delirium (<2%), hypoesthesia (<2%), myoclonus (<2%), nervousness (<2%), paresthesia (<2%), restlessness (<2%)

Dermatologic: Skin rash (4% to 6%), dermal ulcer (3%), ecchymoses (3%), acne vulgaris (<2%), alopecia (<2%), burning sensation of skin (<2%), extravasation reactions (<2%), night sweats (<2%), pruritus (<2%), urticaria (<2%)

Endocrine & metabolic: Hypervolemia (5%), dehydration (3%), hypoglycemia (3%), hirsutism (<2%), hypercalcemia (<2%), hyperkalemia (<2%), hyperparathyroidism (<2%), hyperphosphatemia (<2%), hypocalcemia (<2%), hypoparathyroidism (<2%), increased thirst (<2%), weight loss (<2%)

Gastrointestinal: Vomiting (5% to 8%), gastrointestinal hemorrhage (5%), peritonitis (5%), constipation (4% to 5%), abdominal pain (4%), dyspepsia (3%), xerostomia (3%), decreased appetite (<2%), dysgeusia (<2%), dysphagia (<2%), gastritis (<2%), gastroesophageal reflux disease (<2%)

Genitourinary: Urinary urgency (children and adolescents: 6%), chronic renal failure (3%), uremia (3%), urinary tract infection (3%), erectile dysfunction (<2%), mastalgia (<2%), vaginal infection (<2%)

Hematologic & oncologic: Anemia (<2%), lymphadenopathy (<2%), malignant neoplasm of breast (<2%), prolonged bleeding time (<2%), rectal hemorrhage (<2%)

Hepatic: Abnormal hepatic function tests (<2%), increased serum AST (<2%)

Hypersensitivity: Hypersensitivity reaction (6%)

Infection: Influenza (5%), sepsis (5%)

Local: Pain at injection site (<2%)

Neuromuscular & skeletal: Arthralgia (5%), arthritis (5%), weakness (3% to 5%), back pain (3% to 4%), leg cramps (3%), muscle spasm (3%), joint stiffness (<2%), muscle twitching (<2%), myalgia (<2%)

Ophthalmic: Conjunctivitis (children and adolescents: 6%; adults: <2%), glaucoma (<2%), ocular hyperemia (<2%)

Otic: Otalgia (<2%)

Respiratory: Nasopharyngitis (8%), asthma (children and adolescents: 6%), pneumonia (5%), oropharyngeal pain (4%), bronchitis (3%), cough (3%), sinusitis (3%), dyspnea (<2%), orthopnea (<2%), pulmonary edema (<2%), upper respiratory tract infection (<2%), wheezing (<2%)

Miscellaneous: Fever (3% to 5%), laboratory test abnormality (<2%), swelling (<2%)

<1% (Limited to important or life-threatening): Angioedema (including laryngeal edema), increased serum creatinine

Concerns related to adverse effects:

• Excessive vitamin D: Excessive vitamin D administration may lead to over suppression of PTH, progressive or acute hypercalcemia, hypercalciuria, hyperphosphatemia and adynamic bone disease.

• Hypercalcemia: Progressive and/or acute hypercalcemia may increase risk of cardiac arrhythmias and seizures; chronic hypercalcemia may lead to generalized vascular and other soft-tissue calcification. Phosphate and vitamin D (and its derivatives) should be withheld during therapy to avoid hypercalcemia. Risk of hypercalcemia may be increased by concomitant use of calcium-containing supplements and/or medications that increase serum calcium (eg, thiazide diuretics).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information

See Usual Adult Dose section

See Usual Adult Dose section

See Usual Adult Dose section

This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus. AU TGA pregnancy category: C US FDA pregnancy category: C

Animal studies showed decreased fetal viability, and increased newborn mortality was seen at maternally toxic doses. The drug crossed the placental barrier in an animal model. No teratogenicity was seen, however other vitamin D preparations have led to teratogenesis. There are no controlled data in human pregnancy. AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.