Paricalcitol (paricalcitol)

Paricalcitol dosage must be individualized carefully according to serum or plasma intact parathyroid hormone (iPTH) concentrations and serum calcium and phosphorus concentrations. In patients receiving oral paricalcitol, serum calcium, serum phosphorus, and serum or plasma iPTH concentrations should be monitored at least every 2 weeks for 3 months after initiation of therapy or after subsequent dosage changes, then monthly for 3 months (once the dosage is stabilized), and every 3 months thereafter. The manufacturer recommends that iPTH concentrations be determined every 3 months in patients receiving parenteral paricalcitol; more frequent monitoring may be necessary during dosage adjustments. In addition, the manufacturer recommends that serum calcium and phosphorus concentrations be monitored frequently (e.g., twice weekly) during the initial dosage adjustments and after subsequent dosage changes and at least monthly once the dosage is stabilized in patients receiving parenteral paricalcitol.

If use of a potent inhibitor of the cytochrome P-450 (CYP) 3A isoenzyme (e.g., atazanavir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, the fixed combination of lopinavir and ritonavir (lopinavir/ritonavir), nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) is initiated or discontinued in a patient receiving paricalcitol, serum calcium and iPTH concentrations should be monitored closely; paricalcitol dosage adjustment may be necessary.

Dosage adjustment is not required in patients with mild to moderate hepatic impairment.

Nephrology experts state that the optimal iPTH concentration for patients with stage 3a (estimated glomerular filtration rate (eGFR) 45-59 mL/minute per 1.73 m2) to stage 5 (eGFR less than 15 mL/minute per 1.73 m2) chronic kidney disease (CKD) who are not undergoing dialysis is unknown, but modest increases in iPTH concentration may represent an appropriate adaptive response to declining renal function. For patients with stage 5 CKD undergoing dialysis, some experts suggest that iPTH concentrations may be maintained within a range of approximately 2-9 times the assay's upper limit of normal (ULN) (which may correspond to a range of approximately 130-600 pg/mL for commercially available assays ). Although some clinicians suggest that this range is too broad, available assays for PTH exhibit substantial variability; the previously recommended range of 150-300 pg/mL for patients with stage 5 CKD requiring dialysis was based on an assay that is no longer commercially available. Oversuppression of PTH may increase the risk of adynamic bone disease and should be avoided. (See Uses: Mineral and Bone Disorder Secondary to Chronic Renal Disease, in the Vitamin D Analogs General Statement 88:16.) Nephrology experts currently recommend that the individual values for serum calcium and phosphorus (evaluated together) be used instead of the mathematical construct of calcium times phosphorus product to guide clinical practice.

Paricalcitol is administered orally once daily or 3 times weekly; the drug may be given without regard to meals. When paricalcitol is administered 3 times weekly, the drug should be administered no more frequently than every other day.

Paricalcitol also is administered by direct IV injection at any time during dialysis; the drug should be administered IV no more frequently than every other day.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Oral Phosphates; Active Vitamin D Analogs/Burosumab

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Both burosumab and phosphates or vitamin D may increase serum phosphate levels. This combination may lead to greater increases in serum phosphate than anticipated.

CLINICAL EFFECTS: The combination of burosumab with oral phosphates or active vitamin D analogs may result in hyperphosphatemia and may increase the risk of nephrocalcinosis.(1)

PREDISPOSING FACTORS: Patients with renal impairment have alterations in mineral metabolism that may increase the risk of hyperphosphatemia.(1)

PATIENT MANAGEMENT: The concomitant use of burosumab with oral phosphates or active vitamin D analogs is contraindicated. Discontinue oral phosphate and/or active vitamin D analogs one week before starting burosumab.(1)

DISCUSSION: Burosumab restores dysfunctional renal phosphate reabsorption and renal production of 1,25-dihydroxyvitamin D to treat X-linked hypophosphatemia. Additional oral phosphates and/or active vitamin D analogs may raise serum phosphate higher than anticipated.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Fat Soluble Vitamins/Colesevelam

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1)

CLINICAL EFFECTS: Colesevelam may reduce absorption of fat soluble vitamins, leading to a deficiency state.

PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome.

PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by colesevelam should be borne in mind during implementation of a vitamin supplementation strategy. Oral multivitamin supplements should be taken at least four hours before the dose of colesevelam.(1)

DISCUSSION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1)

Fat Soluble Vitamins/Orlistat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The acetate ester forms of vitamin A and vitamin E must undergo hydrolysis for absorption from the gastrointestinal tract.(1) The enzyme responsible for this hydrolysis is inhibited by orlistat.(2)

CLINICAL EFFECTS: Orlistat may reduce absorption of fat soluble vitamins, leading to a deficiency state.

PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome.

PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by orlistat should be borne in mind during implementation of a vitamin supplementation strategy. Patients should be strongly encouraged to take a multivitamin supplement which contains fat soluble vitamins, particularly Vitamin D as it appears most susceptible to this interaction.(4,5) Multivitamin supplements should be taken at least two hours before or after the dose of orlistat, or at bedtime.(4) Patients with chronic malabsorption syndromes should not receive orlistat.(4)

DISCUSSION: Adult patients taking orlistat without supplementation showed a greater reduction in vitamin A,D,E and beta-carotene levels compared to placebo during two or more consecutive visits in studies of 1-2 years duration; these patients had normal baseline values prior to orlistat therapy. Low vitamin values in orlistat patients were as follows: low Vitamin D 12%, low beta-carotene 6.1%, low Vitamin E 5.8%, low Vitamin A 2.2%.(4) A pharmacokinetic interaction study showed a 30% reduction in beta-carotene supplement absorption and a 60% decreased in vitamin E acetate absorption with concomitant orlistat.(4) In a study, orlistat produced the vitamin net concentration by approximately 43%.(1) In a study, no statistically significant decrease in vitamin A absorption was observed with concurrent orlistat.(2) In a study, mean vitamin D levels were significantly reduced compared with baseline after one month of orlistat therapy despite multivitamin supplementation.(5)

Paricalcitol/Cholestyramine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Cholestyramine may impair intestinal absorption of fat-soluble vitamins. Paricalcitol is an analogue of a fat-soluble vitamin and therefore cholestyramine may interfere with absorption of paricalcitol.(1)

CLINICAL EFFECTS: Concurrent use may result in decreased levels and clinical effects of paricalcitol.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of paricalcitol capsules recommends that paricalcitol be taken at least 1 hour before or 4-6 hours after taking cholestyramine.(1)

DISCUSSION: The manufacturer recommends that administration of paricalcitol capsules be separated from concurrent administration with drugs that impair intestinal absorption of fat-soluble vitamins.(1)

Paricalcitol/Mineral Oil

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Mineral oil may impair intestinal absorption of fat-soluble vitamins. Paricalcitol is an analogue of a fat-soluble vitamin and therefore mineral oil may interfere with absorption of paricalcitol.(1)

CLINICAL EFFECTS: Concurrent use may result in decreased levels and clinical effects of paricalcitol.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of paricalcitol capsules recommends that paricalcitol be taken at least 1 hour before or 4-6 hours after taking mineral oil.(1)

DISCUSSION: The manufacturer recommends that administration of paricalcitol capsules be separated from concurrent administration with drugs that impair intestinal absorption of fat-soluble vitamins.(1)

There is no enhanced messaging for this drug.

• Hypervitaminosis D

• Hypercalcemia
• Hyperphosphatemia

• Digitalis toxicity

There is no enhanced messaging for this drug.

More Frequent

• Hypertension
• Skin rash
• Vertigo

Less Frequent

• Arthritis
• Bacterial sepsis
• Chest pain
• Dehydration
• Fungal infection
• Gastrointestinal hemorrhage
• Hypervolemia
• Hypoglycemic disorder
• Hypotension
• Pneumonia
• Skin ulcer
• Urinary tract infection

Rare or Very Rare

• Abnormal hepatic function tests
• Adynamic bone disease
• Anemia
• Angioedema
• Anorexia
• Atrial flutter
• Cardiac arrest
• Cardiac arrhythmia
• Cardiac arrhythmia
• Cerebrovascular accident
• Glaucoma
• Hypercalcemia
• Hypercalcemia
• Hyperkalemia
• Hyperphosphatemia
• Hypertension
• Hypocalcemia
• Hypoparathyroidism
• Hypotension
• Laryngeal edema
• Pulmonary edema
• Rectal bleeding
• Syncope

More Frequent

• Diarrhea
• Dizziness
• Edema
• Nausea
• Nausea
• Sore throat
• Vomiting
• Vomiting

Less Frequent

• Abdominal pain with cramps
• Back pain
• Chills
• Constipation
• Cough
• Cramps in legs
• Depression
• Edema
• Fever
• Headache disorder
• Insomnia
• Malaise
• Muscle spasm
• Pain
• Palpitations
• Pruritus of skin
• Sinusitis
• Symptoms of anxiety
• Xerostomia

Rare or Very Rare

• Acne vulgaris
• Acute abdominal pain
• Acute cognitive impairment
• Agitation
• Alopecia
• Anorexia
• Arthralgia
• Chest pain
• Conjunctival hyperemia
• Conjunctivitis
• Conjunctivitis
• Constipation
• Cough
• Delirium
• Diarrhea
• Dizziness
• Dysgeusia
• Dysgeusia
• Dysphagia
• Dyspnea
• Earache
• Erectile dysfunction
• Facial edema
• Fatigue
• Gait abnormality
• Gastritis
• General weakness
• Headache disorder
• Hirsutism
• Hypoesthesia
• Influenza
• Injection site sequelae
• Insomnia
• Lymphadenopathy
• Mastalgia
• Mastalgia
• Muscle fasciculation
• Myalgia
• Myoclonus
• Nervousness
• Night sweats
• Pain
• Paresthesia
• Pharyngitis
• Photophobia
• Polydipsia
• Pruritus of skin
• Skin rash
• Syncope
• Upper respiratory infection
• Urticaria
• Urticaria
• Wheezing
• Xerostomia

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.