Conventional paclitaxel

Several regimens of paclitaxel, alone or in combination with other antineoplastics, are in use. Doses vary, depending on the regimen used. Consult literature. ■ For all uses, premedication, specific parameters, and specific equipment are required before or during administration; see Premedication, Dose Adjustments, and Precautions/Monitor.

Abraxane

Conventional paclitaxel

Reduce dose by 20% for subsequent courses in patients who experience severe peripheral neuropathy or severe neutropenia (neutrophils less than 500 cells/mm³) for 1 week or longer. ■ Withhold therapy if neutrophils below 1,500/mm³ or platelets below 100,000/mm³. ■ Dose reduction not required in impaired renal function. ■ In AIDS-related Kaposi’s sarcoma the parameters are slightly different. Initiate or repeat paclitaxel only if neutrophil count is equal to or greater than 1,000/mm³; reduce dose of dexamethasone to 10 mg/dose; reduce dose of paclitaxel by 20% in patients who experience severe neutropenia (neutrophils less than 500/mm³ for a week or longer); use concomitant filgrastim (G-CSF) as clinically indicated. ■ Recommendations for dose adjustment of the initial course of therapy in patients with impaired hepatic function are listed in the following chart.

Abraxane

Adjustment of starting dose is not necessary in patients with mild to moderate renal impairment (CrCl equal to or greater than 30 to less than 90 mL/min). ■ Withhold therapy in all patients if neutrophils below 1,500/mm³. ■ In patients with MBC, withhold therapy if platelets below 100,000/mm³. ■ For MBC, reduce dose to 220 mg/M² in patients who experience severe neutropenia (neutrophils less than 500 cells/mm³ for 7 days or more) or severe sensory neuropathy. Further reduce dose to 180 mg/M² for subsequent courses if severe neutropenia (less than 500 cells/mm³ for 7 days or more) or severe sensory neuropathy recurs. ■ If Grade 3 sensory neuropathy occurs, withhold treatment until resolution to Grade 1 or 2 for MBC or until resolution to less than or equal to Grade 1 for NSCLC, followed by a dose reduction for all subsequent courses. ■ No dose adjustment is necessary for patients with mild hepatic impairment (total bilirubin greater than ULN and less than or equal to 1.5 times the ULN and AST less than or equal to 10 times the ULN), regardless of indication. ■ Do not administer Abraxane to patients with total bilirubin greater than 5 times the ULN or AST greater than 10 times the ULN regardless of indication because these patients have not been studied. ■ Do not administer Abraxane to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment. ■ Recommendations for a starting dose in patients with hepatic impairment are shown in the following chart. Doses for subsequent cycles should be based on patient tolerance.

■ In patients with NSCLC who develop severe neutropenia or thrombocytopenia, withhold therapy until counts recover to an ANC of at least 1,500 cells/mm³ and platelets of at least 100,000 cells/mm³ on Day 1 or to an ANC of at least 500 cells/mm³ and platelets of at least 50,000 cells/mm³ on Day 8 or 15 of the cycle. Upon resumption of dosing, follow dose reduction outlined in the following chart.

■ Dose-level reductions for patients with adenocarcinoma of the pancreas are outlined in the following chart.

■ Dose modifications for neutropenia and/or thrombocytopenia for patients with adenocarcinoma of the pancreas are provided in the following chart.

■ Dose modifications for other adverse reactions for patients with adenocarcinoma of the pancreas are provided in the following chart.

Conventional paclitaxel

Must be diluted and given as an infusion. May leach the toxic plasticizer DEHP from PVC infusion bags or sets; prepare and store in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administer through polyethylene-lined administration sets. Compatible with NS, D5W, D5NS, or D5R. Final concentration of 0.3 to 1.2 mg/mL required. For a 135 mg/M² dose, a large adult (body surface about 2 M²) will receive 270 mg (45 mL of paclitaxel at 6 mg/mL). Will require dilution in an additional 180 mL to make a 1.2 mg/mL concentration or in an additional 855 mL to make a 0.3 mg/mL concentration. Solution may appear hazy. Do not use a chemo-dispensing pin; can cause the stopper to collapse and result in loss of sterility.

Abraxane

Available in single-use vials, each containing 100 mg (5 mg/mL after reconstitution with 20 mL of NS). Calculate the exact number of vials needed to achieve the total dosing volume of suspension required.

Total # of vials required = Total dose (mg) ÷ 100 mg

Dosing volume (mL) = Total dose (mg) ÷ 5 (mg/mL)

For example, a MBC patient with a body surface area (BSA) of 1.73 M² would need a dose of 449.8 mg of Abraxane. 449.8 mg divided by 100 mg equals 4.498 vials, so 5 vials of Abraxane would be needed. 449.8 mg divided by 5 (mg/mL) equals a dosing volume of 90 mL of reconstituted solution.

Reconstitute each 100-mg vial with 20 mL of NS. A specific process is required to avoid foaming or clumping. Over a minimum of 1 minute, slowly inject the NS, directing it to the inside wall of the vial. Do not allow the NS to flow directly onto the lyophilized cake (will cause foaming). Allow each vial to sit for a minimum of 5 minutes while the NS wets the cake. Gently swirl and/or invert each vial slowly for at least 2 minutes until complete dissolution. Avoid generation of foam. If foaming or clumping occurs, allow solution to stand for at least 15 minutes until foam subsides. Solution should be milky and homogenous without visible particulates. If particulates are visible, gently invert to ensure complete resuspension before use.

Withdraw the calculated volume and inject into an empty sterile polyvinyl chloride (PVC) container or a PVC or non–PVC-type infusion bag (a total dosing volume of 90 mL in the previous example). The use of medical devices containing silicone oil as a lubricant (i.e., syringes and IV bags) to reconstitute and administer Abraxane may result in the formation of proteinaceous strands. Discard suspension if proteinaceous strands, particulate matter, or discoloration are observed.

Conventional paclitaxel

Leaches out plasticizers; see Dilution.

One source suggests the following compatibilities:

Conventional paclitaxel

Abraxane

Manufacturer states, “Use of specialized DEHP-free solution containers or administration sets is not necessary.” The use of medical devices containing silicone oil as a lubricant (i.e., syringes and IV bags) to reconstitute and administer Abraxane may result in the formation of proteinaceous strands. Additional specific information not available.

Conventional paclitaxel

A single dose properly diluted must be equally distributed over 3 hours or as indicated in Usual Dose. Use of an in-line filter not greater than 0.22 microns required. Use a metriset (60 gtt/mL) or an infusion pump appropriate to control flow. Rate extended to 24 hours in some regimens.

Abraxane

A single dose properly reconstituted and equally distributed over 30 minutes.

All formulations

An antineoplastic. A novel antimicrotubule inhibitor. Paclitaxel derived from the bark of Pacific yew has now been replaced by paclitaxel produced semi-synthetically from a renewable source (needles and twigs of the Himalayan yew). Both are chemically identical. Through specific processes it stabilizes microtubules by preventing depolymerization. This action inhibits the normal dynamic reorganization of the microtubule network essential for vital interphase and mitotic cellular functions. Also induces abnormal bundles of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Distribution and/or tissue binding is extensive. Evidence suggests metabolism in the liver via the cytochrome P₄₅₀ isoenzyme system (CYP2C8 and CYP3A4). Terminal half-life ranges from 13.1 to 27 hours. Excreted primarily as metabolites in feces and, to a lesser extent, in urine.

Conventional paclitaxel

More active in patients who have not received previous chemotherapy.

Abraxane

Consists of albumin-bound paclitaxel nanoparticles. Highly bound to serum proteins; metabolized in the liver, primarily by CYP2C8 and, to a lesser extent, by CYP3A4. Terminal half-life ranges from 13 to 27 hours. Minimal excretion in urine and feces.

Conventional paclitaxel

First-line and subsequent therapy for the treatment of advanced carcinoma of the ovary. ■ First-line treatment for ovarian cancer in combination with cisplatin. ■ Adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy. Most effective in estrogen- and progesterone-receptor–negative tumors. ■ Metastatic breast cancer refractory to initial chemotherapy or for a relapse within 6 months. ■ First-line treatment, in combination with cisplatin, for non–small-cell lung cancer in patients who are not candidates for potentially curative surgery or radiation therapy. ■ Second-line treatment of AIDS-related Kaposi’s sarcoma.

Abraxane

Treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. ■ First-line treatment of locally advanced or metastatic non–small-cell lung cancer (NSCLC) (in combination with carboplatin) in patients who are not candidates for curative surgery or radiation therapy. ■ First-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.

Conventional paclitaxel

Baseline neutropenia less than 1,500 cells/mm³ in patients with solid tumors or baseline neutropenia less than 1,000 cells/mm³ in patients with AIDS-related Kaposi’s sarcoma. History of prior severe hypersensitivity reactions to paclitaxel or other drugs formulated in polyoxyethylated castor oil (Cremophor EL [e.g., cyclosporine, teniposide]).

Abraxane

Baseline neutrophil count less than 1,500 cells/mm³. ■ Patients who experience a severe hypersensitivity reaction to Abraxane should not be rechallenged with the drug.

All formulations

Follow guidelines for handling cytotoxic agents. See Appendix A, p. 1331. ■ Usually administered by or under the direction of the physician specialist in a facility with adequate diagnostic and treatment facilities to monitor the patient and respond to any medical emergency.

Conventional paclitaxel

Use caution in patients with cardiac conduction abnormalities, CHF, and MI within previous 6 months. ■ Bradycardia, hypertension, and hypotension have been observed but rarely required treatment. Occasionally the infusion must be interrupted or discontinued because of initial or recurrent hypertension; see Monitor. ■ Pre-existing neuropathies resulting from prior therapies are not a contraindication for paclitaxel therapy. ■ Various studies show that incidence and severity of neurotoxicity and hematologic toxicity increase with dose, especially above 190 mg/M². ■ Use with caution in patients with a total bilirubin greater than 2 times the ULN. May be at increased risk of toxicity, especially profound myelosuppression; see Dose Adjustments. ■ See Drug/Lab Interactions.

Abraxane

Do not substitute for or with other paclitaxel formulations. ■ Use of gloves recommended. Wash skin immediately if contact occurs. Flush mucous membranes thoroughly with water if contact occurs. Topical exposure may result in tingling, burning, and redness. ■ Premedication to prevent hypersensitivity reactions is not required but may be needed in patients who have had a prior hypersensitivity reaction to Abraxane. Reports of severe and sometimes fatal hypersensitivity reactions have occurred; see Contraindications; do not rechallenge patients who have had a severe reaction. ■ Neutropenia is dose dependent and is a dose-limiting toxicity. Do not administer Abraxane to patients with a baseline absolute neutrophil count (ANC) of less than 1,500 cells/mm³; see Dose Adjustments. ■ Sensory neuropathy is dose dependent and schedule dependent and occurs frequently; see Dose Adjustments. ■ Sepsis occurred in 5% of patients, with or without neutropenia, who received Abraxane in combination with gemcitabine. Biliary obstruction or the presence of a biliary stent were risk factors for severe or fatal sepsis. ■ Pneumonitis, including some cases that were fatal, has been reported in patients receiving Abraxane in combination with gemcitabine; see Antidote. ■ Has not been studied in patients with severe renal dysfunction or end-stage renal disease. ■ Use with caution in patients with hepatic impairment. May be at increased risk for toxicity, particularly myelosuppression; see Dose Adjustments. ■ Derived from human albumin; may carry a risk of transmission of viral disease or Creutzfeldt-Jakob disease; risk considered extremely remote. ■ Has not been studied in patients who have had a hypersensitivity reaction to conventional paclitaxel.

All formulations

Do not administer chloroquine or live virus vaccines to patients receiving antineoplastic agents.

Conventional paclitaxel

Formal drug interaction studies have not been conducted. To reduce potential for profound myelosuppression when using paclitaxel and cisplatin concurrently, give paclitaxel first, then cisplatin. ■ Neurotoxicity and symptomatic motor dysfunction occurring with higher doses (greater than 250 mg/M²) may be potentiated by cisplatin and filgrastim (G-CSF). ■ May cause additive effects with bone marrow–suppressing agents, radiation therapy, or agents that cause blood dyscrasias (e.g., amphotericin B, antithyroid agents [methimazole (Tapazole)], azathioprine, chloramphenicol, ganciclovir [Cytovene], interferon, plicamycin [Mithracin], zidovudine [AZT, Retrovir]). Reduced doses may be required. ■ May increase levels of doxorubicin and its active metabolite when drugs are used in combination. ■ Metabolized by cytochrome P₄₅₀ isoenzymes CYP3A4 and CYP2C8. Use caution when administered concomitantly with known substrates (e.g., buspirone [BuSpar], eletriptan [Relpax], felodipine [Plendil], lovastatin [Mevacor], midazolam [Versed], sildenafil [Viagra, Revatio], simvastatin [Zocor], and triazolam [Halcion]), inhibitors (e.g., atazanavir [Reyataz], clarithromycin [Biaxin], indinavir [Crixivan], itraconazole [Sporanox], ketoconazole [Nizoral], nefazodone, nelfinavir [Viracept], ritonavir [Norvir], saquinavir [Invirase], and telithromycin [Ketek]), and inducers (e.g., rifampin [Rifadin] and carbamazepine [Tegretol]) of CYP3A4. ■ Other medications that are substrates and/or inducers of CYP3A4 (e.g., ritonavir [Norvir], saquinavir [Invirase], indinavir [Crixivan], and nelfinavir [Viracept]) may alter the metabolism of paclitaxel but have not been evaluated in clinical trials. ■ Use caution when administered concomitantly with known substrates (e.g., repaglinide [Prandin], rosiglitazone [Avandia]), inhibitors (e.g., gemfibrozil [Lopid]), and inducers (e.g., rifampin [Rifadin]) of CYP2C8. ■ Dexamethasone (Decadron), diphenhydramine (Benadryl), cimetidine (Tagamet), and ranitidine (Zantac) do not affect the protein binding of paclitaxel.

Abraxane

Drug interaction studies have not been conducted. See All Formulations above. ■ Use caution when administering with medicines known to inhibit or induce CYP2C8 or CYP3A4. Drugs that may inhibit these enzymes include ketoconazole (Nizoral) and other imidazole antifungals, erythromycin, fluoxetine (Prozac), gemfibrozil (Lopid), cimetidine (Tagamet), ritonavir (Norvir), saquinavir (Invirase), indinavir (Crixivan), and nelfinavir (Viracept). Drugs that may induce these enzymes include rifampin (Rifadin), carbamazepine (Tegretol), phenobarbital, phenytoin (Dilantin), efavirenz (Sustiva), nevirapine (Viramune).

Conventional paclitaxel

Dose dependent and generally reversible, but may be fatal. All patients were premedicated to prevent hypersensitivity reactions. Abnormal ECG, alopecia, arthralgia/myalgia, asthenia, autonomic neuropathy resulting in paralytic ileus, bleeding, bone marrow suppression (anemia, leukopenia, neutropenia, thrombocytopenia), bradycardia, CHF (including cardiac dysfunction and reduction in left ventricular ejection fraction or ventricular failure [more common in patients receiving combination therapy with anthracyclines]), diarrhea, elevated alkaline phosphatase, elevated AST, elevated bilirubin, febrile neutropenia, fever, fluid retention and edema, hypersensitivity reactions (moderate [e.g., dyspnea, flushing, hypotension, rash, tachycardia]; severe [e.g., chest pain, dyspnea requiring bronchodilators, hypotension requiring treatment, generalized urticaria]), hypertension, hypotension, infections including opportunistic infections (chills, fever, night sweats), injection site reactions (cellulitis, fibrosis, induration, necrosis, phlebitis, skin exfoliation), mucositis, nausea and vomiting, numbness, optic nerve and/or visual disturbances, peripheral neuropathy, respiratory reactions (interstitial pneumonia, lung fibrosis, pleural effusions, pulmonary embolism, respiratory failure), Stevens-Johnson syndrome, toxic epidermal necrolysis, and visual disturbances. A grand mal seizure occurred in one patient. Other side effects (e.g., cardiac arrest, cardiac ischemia/infarction, CVA, hepatic necrosis, and hepatic encephalopathy leading to death; intestinal obstruction; intestinal perforation; ischemic colitis; pancreatitis; thrombosis/embolism) have been reported rarely. A higher incidence of elevated liver function tests and renal toxicity is seen in Kaposi’s sarcoma patients.

Abraxane

Usual dose

Administered as an IV bolus injection for 3 consecutive days before and 3 consecutive days after myelotoxic therapy (a total of 6 doses). Do not administer within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Has resulted in increased severity and duration of oral mucositis. Myelotoxic therapy is high-dose chemotherapy, with or without radiation, that is destructive to bone marrow or any of its components. Followed by bone marrow transplant/hematopoietic stem cell support.

Dose adjustments

None indicated. Gender-related differences were not observed. ■ No dose adjustment is recommended in impaired renal function. ■ Pharmacokinetic studies have not been performed for pediatric patients or for patients with hepatic insufficiency.

Dilution

Available as a lyophilized powder in a 6.25-mg single vial. Reconstitute by slowly injecting 1.2 mL SWFI into vial. Final concentration is 5 mg/mL. Swirl contents gently. Do not shake. Dissolution should take less than 3 minutes. Solution is clear and colorless. Do not use if particulates are present or if solution is discolored.

Compatibility

Specific information not available; however, manufacturer states, “If heparin is used to maintain an IV line, saline should be used to flush the line before and after administration since palifermin has been shown to bind to heparin in vitro.”

Rate of administration

A single dose administered as an IV bolus injection. If heparin is used to maintain an IV line, flush the line with NS before and after administration.

Actions

Human keratinocyte growth factor (KGF) produced by recombinant DNA technology. Binding of KGF to its receptor results in proliferation, differentiation, and migration of epithelial cells. KGF receptors are present on the epithelial cells in many tissues, including the tongue, buccal mucosa, esophagus, stomach, intestine, salivary gland, lung, liver, pancreas, kidney, bladder, mammary gland, skin (hair follicles and sebaceous gland), and the lens of the eye. The KGF receptor is not present on the cells of the hematopoietic lineage. KGF stimulates the growth of cells in tissues such as the skin and the epithelial layer of the mouth, stomach, and colon. Protects the epithelial cells that line the mouth and GI tract from the damage caused by chemotherapy and radiation and stimulates the growth and development of new epithelial cells. Average half-life is 4.5 hours (range: 3.3 to 5.7 hours).

Indications and uses

To decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies who are receiving myelotoxic therapy (high-dose chemotherapy), with or without radiation therapy, and who require hematopoietic stem cell support. Indicated as supportive care for preparative regimens predicted to result in equal to or greater than WHO Grade 3 mucositis in the majority of patients.

Contraindications

Manufacturer states, “None.”

Precautions

Safety and efficacy have not been established in patients with nonhematologic malignancies. Effect of palifermin on stimulation of KGF receptor–expressing, nonhematopoietic tumors in patients is not known. There is some evidence of tumor growth and stimulation in cell cultures and in animal models of nonhematopoietic human tumors.

Drug/lab interactions

Formal studies have not been conducted. ■ Interacts with unfractionated as well as low-molecular-weight heparins (e.g., enoxaparin [Lovenox]). When coadministered, there was no significant effect of palifermin on heparin activity with respect to aPPT. However, coadministration resulted in an increased palifermin AUC and a decreased palifermin clearance, volume of distribution, and half-life. If heparin is used to maintain an IV line, NS should be used to flush the line before and after palifermin administration. ■ Do not administer within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Has resulted in increased severity and duration of oral mucositis.

Side effects

The most common serious side effects are fever, GI events, respiratory events, and skin rash. Other commonly reported reactions include arthralgia, edema, elevated serum amylase and lipase, hypertension, oral toxicities (alteration of taste, oral/perioral dysesthesia, tongue discoloration, tongue thickening), pain, paresthesia, proteinuria, and skin toxicities (erythema, pruritus, rash). Has the potential for immunogenicity, but the clinical significance is unknown.

Antidote

Notify physician of all side effects. Most will be treated symptomatically.

Usual dose

Pediatric dose

Dose adjustments

No dose adjustment required based on age or race or in patients with any degree of renal or hepatic impairment.

Dilution

Available in 0.25 mg/5 mL and 0.075 mg/1.5 mL single-use vials. May be given undiluted.

Compatibility (underline indicates conflicting compatibility information)

Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.

Manufacturer states, “Should not be mixed with other drugs. Flush the infusion line with NS before and after administration.”

One source suggests the following compatibilities:

Rate of administration

Flush the infusion line with NS before and after administration.

Actions

A long-acting (up to 120 hours [5 days]) antinauseant and antiemetic agent. A selective antagonist of specific serotonin (5HT₃) receptors. Has a strong binding affinity for this receptor and little or no affinity for other receptors. Chemotherapeutic agents such as cisplatin increase the release of serotonin from specific cells in the GI tract, causing emesis. Postoperative nausea and vomiting is also triggered by the release of serotonin. By antagonizing serotonin receptors both on the vagus nerve in the periphery and centrally in the chemoreceptor trigger zone, the incidence and severity of chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting are decreased. 62% bound to plasma protein. Partially metabolized by multiple CYP enzymes; however, palonosetron is not an inhibitor or an inducer of CYP enzyme activity. Eliminated slowly from the body through both metabolic pathways and renal excretion. Has a prolonged half-life of approximately 40 hours. 80% of a single dose was recovered in urine within 144 hours.

Indications and uses

Prevention of acute nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy in pediatric patients 1 month to less than 17 years of age and in adults. ■ Prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy in adults. Studies identified cisplatin in doses equal to or greater than 70 mg/M² and cyclophosphamide (Cytoxan) in doses equal to or greater than 1,100 mg/M² as highly emetogenic. Studies identified cisplatin in doses equal to or less than 50 mg/M², cyclophosphamide in doses less than 1,100 mg/M², doxorubicin (Adriamycin) in doses greater than 25 mg/M², methotrexate in doses greater than 250 mg/M², and carboplatin (Paraplatin), epirubicin (Ellence), and irinotecan (Camptosar) in standard doses as moderately emetogenic. ■ Prevention of postoperative nausea and vomiting (PONV) in adults for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated.

Contraindications

Known hypersensitivity to palonosetron or any of its components. ■ See Precautions.

Precautions

Hypersensitivity reactions, including anaphylaxis, have been reported with or without known hypersensitivity to other 5-HT₃ receptor antagonists. Cross-sensitivity may occur with other selective 5-HT₃ receptor antagonists (e.g., dolasetron [Anzemet], granisetron [Kytril], ondansetron [Zofran]). ■ Serotonin syndrome has been reported with 5-HT₃ receptor antagonists. Most reports were associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors [e.g., paroxetine (Paxil), escitalopram (Lexapro)], serotonin and norepinephrine reuptake inhibitors [e.g., duloxetine (Cymbalta), venlafaxine (Effexor XR)], monoamine oxidase inhibitors [e.g., selegiline (Eldepryl)], mirtazapine [Remeron], fentanyl, lithium, tramadol [Ultram], and intravenous methylene blue). Some cases were fatal. ■ Routine prophylaxis is not recommended for patients in whom there is little expectation of PONV. However, for patients in whom nausea and vomiting must be avoided during the postoperative period, prophylaxis is recommended even when the incidence of PONV is low. ■ Palonosetron does not appear to have any effect on ECG intervals, including QT_C duration.

Drug/lab interactions

Eliminated through both renal excretion and metabolic pathways. Does not induce or inhibit the cytochrome P₄₅₀ drug metabolizing system; potential for clinically significant drug interactions is considered to be low. ■ Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been reported following the concomitant use of 5-HT₃ receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs); see Precautions. ■ Has been safely administered with analgesics, antiemetics/antinauseants, antispasmodics, anticholinergic agents, and corticosteroids. ■ Has been safely administered with PO metoclopramide (10 mg 4 times daily). ■ Has been administered with oral aprepitant (Emend). ■ Does not appear to inhibit the antitumor activity of emetogenic cancer chemotherapies (cisplatin, cyclophosphamide, cytarabine, doxorubicin, and mitomycin C have been tested in murine tumor models). ■ See Precautions.

Side effects

Antidote

Most side effects will be treated symptomatically. Keep physician informed. There is no specific antidote. If symptoms of serotonin syndrome occur, discontinue palonosetron and initiate supportive care. Has a large volume of distribution; dialysis not likely to be effective in overdose. Treat hypersensitivity reactions and resuscitate as indicated.

Usual dose

Prehydration required. Do not exceed a 90-mg dose. See Precautions and Monitor.

Dose adjustments

Accumulation of pamidronate in renally impaired patients is not anticipated if dosed on a monthly schedule. No experience with creatinine above 5 mg/100 mL (1 dL) or in severe hepatic disease. ■ See Precautions and Elderly.

Dilution

Reconstitute each 30- or 90-mg vial with 10 mL SWFI. Dissolve completely (3 or 9 mg/mL).

Compatibility

Manufacturer states, “Should be given in a single intravenous solution and line separate from all other drugs, and do not mix with calcium-containing solutions (e.g., Ringer’s solutions).”

Rate of administration

Use of a microdrip (60 gtt/mL) or an infusion pump recommended for even distribution. Do not exceed recommended rate of infusion. Duration should be no less than 2 hours. Too-rapid infusion rate may lead to overdose, elevated BUN and creatinine levels, and renal tubular necrosis. Rate recommendations vary considerably. They are based on specific clinical trials for each diagnosis. In some trials a rate of up to 1 mg/min has been used with caution.

Actions

A bisphosphonate hypocalcemic agent. Reduces serum calcium concentrations by inhibiting bone resorption. Binds to preformed bone surfaces and may block bone mineral dissolution. May also inhibit osteoclast activity. Effectively inhibits accelerated bone resorption resulting from osteoclast hyperactivity induced by various tumors. Does not inhibit bone formation and mineralization. Some reduction in calcium levels seen in 24 to 48 hours, and maximum response in 4 to 7 days. Rapidly adsorbed by bone. Is not metabolized. Half-life is approximately 21 to 35 hours. Slowly excreted in urine.

Indications and uses

Treatment of moderate to severe hypercalcemia of malignancy in patients with or without bone metastasis, in conjunction with adequate hydration. Symptoms of hypercalcemia may include anorexia, bone pain, confusion, constipation, dehydration, depression, fatigue, lethargy, muscle weakness, nausea and vomiting, and polyuria. Severe dehydration may lead to renal insufficiency. With high levels of serum calcium, cardiac manifestations (e.g., bradycardia, cardiac arrest, ventricular arrhythmias) and neurologic symptoms (e.g., coma, seizures, and death) may occur. ■ Treatment of Paget’s disease. ■ Adjunct in treatment of osteolytic lesions of multiple myeloma and osteolytic bone metastases of breast cancer.

Contraindications

Hypersensitivity to pamidronate or other bisphosphonates (e.g., alendronate [Fosamax], risedronate [Actonel], zoledronic acid [Reclast, Zometa]).

Precautions

Calcium is bound to albumin. Total serum calcium levels in patients who have hypercalcemia of malignancy may not reflect the severity of the hypocalcemia because concomitant hypoalbuminemia is commonly present. Measurement with ionized calcium levels is preferred. If unavailable, all calcium measurement should be corrected for albumin to establish a basis for treatment and evaluation of treatment. ■ Mild or asymptomatic hypercalcemia will be treated with conservative measures (e.g., saline hydration, with or without diuretics [after correcting hypovolemia]). Consider patient’s cardiovascular status. Corticosteroids may be indicated if the underlying cancer is sensitive (e.g., hematologic cancers). ■ May be used adjunctively with chemotherapy, radiation, or surgery. ■ May cause renal toxicity. Deterioration in renal function progressing to renal failure has been reported and has occurred after the initial or a single dose of pamidronate. Patients with pre-existing renal impairment may be at increased risk for developing toxicity. Do not exceed dose of 90 mg. ■ Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates. The majority of cases have been in cancer patients. Risk factors include cancer, concomitant therapy (e.g., chemotherapy, radiotherapy, corticosteroids), and comorbid conditions (e.g., anemia, coagulopathies, infection, pre-existing oral disease). Literature and case reports suggest a higher frequency of ONJ based on tumor type (breast cancer, multiple myeloma) and dental status (dental extraction, periodontal disease, local trauma, including poorly fitting dentures). Cancer patients should maintain good oral hygiene. Consider dental exam and appropriate preventive dentistry before beginning therapy with bisphosphonates. Avoid invasive dental procedures during bisphosphonate therapy. Dental surgery may exacerbate ONJ in patients who develop ONJ while on bisphosphonate therapy. ■ Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported rarely. Onset of symptoms varied from one day to several months after beginning treatment with pamidronate. In most cases, pain resolves when pamidronate is discontinued; however, in some patients symptoms resolved slowly or persisted. ■ Atypical subtrochanteric and diaphyseal femoral fractures have been reported. May occur after minimal or no trauma. Risk may be increased in patients receiving concurrent glucocorticoids (e.g., dexamethasone, prednisone). ■ May be at risk for anemia, leukopenia, or thrombocytopenia; see Monitor. ■ Patients with a history of thyroid surgery may have relative hypoparathyroidism that may predispose them to hypocalcemia with pamidronate.

Drug/lab interactions

Use caution when administered with other potentially nephrotoxic drugs (e.g., aminoglycosides [amikacin, tobramycin, gentamicin], cisplatin). ■ Concurrent administration with furosemide (Lasix) does not affect calcium-lowering action of pamidronate. ■ Does not interfere with any known primary cancer therapy. ■ Effects may be antagonized by calcium-containing preparations or vitamin D; avoid use. ■ Concurrent use with thalidomide (Thalomid) may increase risk of renal toxicity in patients with multiple myeloma.

Side effects

Antidote

Keep physician informed of side effects. Some may respond to symptomatic treatment. Magnesium, phosphorus, and potassium may require replacement if depletion too severe. If mild, all will probably return toward normal in 7 to 10 days. For asymptomatic or mild to moderate hypocalcemia (6.5 to 8 mg/100 mL [1 dL] corrected for serum albumin), short-term calcium therapy (e.g., calcium gluconate) may be indicated. Consider discontinuing pamidronate in patients who develop atypical fractures of the femur. Unknown if risk continues after stopping treatment. Discontinue drug for any symptoms of overdose. Monitor serum calcium and use vigorous IV hydration, with or without diuretics, for 2 to 3 days. Monitor intake and output to ensure adequacy and balance. Use short-term IV calcium therapy if indicated. High fever may respond to steroids. RBC transfusions may be required in anemia. Treat anaphylaxis and resuscitate as indicated.

Usual dose

Neonatal dose

Dose adjustments

See Drug/Lab Interactions; marked reduction of pancuronium dose may be required. ■ A higher total dose may be required in biliary or hepatic disease, but onset is slower and neuromuscular block is prolonged. ■ Clearance decreased and half-life increased in renal insufficiency. One source recommends administering 50% of a dose if CrCl is between 10 and 50 mL/min; do not use if CrCl is less than 10 mL/min.

Dilution

May be given undiluted or diluted in D5W, D5/¹/₂NS, D5NS, NS, or LR for use as an infusion.

Compatibility (underline indicates conflicting compatibility information)

Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.

One source suggests the following compatibilities:

Rate of administration

Actions

A skeletal muscle relaxant. Causes paralysis by interfering with neural transmission at the myoneural junction. Onset of action is dose dependent. Peak effect occurs in 3 to 4 minutes and lasts 30 to 45 minutes. It may take another 30 minutes or up to several hours before complete recovery occurs. Excreted in the urine.

Indications and uses

Adjunctive to general anesthesia to facilitate endotracheal intubation and to relax skeletal muscles during surgery or mechanical ventilation.

Contraindications

Known hypersensitivity to pancuronium or bromides; first trimester of pregnancy.

Precautions

Usually administered by or under the direct observation of the anesthesiologist. Appropriate emergency drugs and equipment for monitoring the patient and responding to any medical emergency must be readily available. ■ Severe anaphylactic reactions have been reported with neuromuscular blocking agents; some have been fatal. Use caution in patients who have had an anaphylactic reaction to another neuromuscular blocking agent (depolarizing or nondepolarizing); cross-reactivity has occurred. ■ Repeated doses may produce a cumulative effect. ■ Impaired pulmonary function or respiratory deficiencies can cause critical reactions. ■ Use caution in impaired liver or kidney function, in patients with tachycardia, and in any patient who might develop adverse effects from an increase in HR. ■ Myasthenia gravis increases sensitivity to drug. ■ Long-term use (i.e., intensive care) may result in prolonged paralysis or skeletal muscle weakness. ■ Acid-base and/or electrolyte imbalance, debilitation, hypoxic episodes, and/or the use of other drugs (e.g., broad-spectrum antibiotics, narcotics, steroids) may prolong the effects of pancuronium.

Drug/lab interactions

May cause severe arrhythmias with inhalant anesthetics (e.g., enflurane, halothane) and in patients on chronic tricyclic antidepressant therapy (e.g., amitriptyline [Elavil]). ■ Potentiated by hypokalemia, some carcinomas, many antibiotics (e.g., aminoglycosides [kanamycin, gentamicin], bacitracin, colistin [Coly-Mycin S], colistimethate [Coly-Mycin M], polymyxin-B [Aerosporin], tetracyclines, piperacillin), calcium salts, CO₂, diuretics, diazepam (Valium) and other muscle relaxants, digoxin, magnesium sulfate, quinidine, morphine, lidocaine, meperidine, propranolol (Inderal), succinylcholine, and others. May need to reduce dose of pancuronium; use with caution. ■ Recurrent paralysis may occur with quinidine. ■ Effects may be decreased by acetylcholine, aminophylline, anticholinesterases, azathioprine, carbamazepine, and potassium. ■ Succinylcholine must show signs of wearing off before pancuronium is given. Use caution.

Side effects

Increased HR, decrease in mean arterial pressure, prolonged action resulting in respiratory insufficiency or apnea and tachycardia. Airway closure caused by relaxation of epiglottis, pharynx, and tongue muscles. Hypersensitivity reactions are possible. Anaphylaxis, histamine release (e.g., bronchospasm, vasodilation, hypotension, cutaneous flushing), and shock may occur. Muscular weakness and atrophy may occur with long-term use (1 to 3 weeks).

Antidote

All side effects are medical emergencies. Treat symptomatically. Controlled artificial ventilation must be continuous. Pyridostigmine (Regonol) or neostigmine given with atropine will probably reverse the muscle relaxation. Not effective in all situations; may aggravate severe overdose. Resuscitate as necessary.

Usual dose

Dose adjustments

Upon the first occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of panitumumab. If the reaction improves to less than Grade 3, reinitiate panitumumab at the original dose. ■ Upon the second occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of panitumumab. If the reaction improves to less than Grade 3, reinitiate panitumumab at 80% of the original dose. ■ Upon the third occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of panitumumab. If the reaction improves to less than Grade 3, reinitiate panitumumab at 60% of the original dose. ■ Upon the fourth occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, permanently discontinue panitumumab. ■ Permanently discontinue panitumumab following the occurrence of a Grade 4 dermatologic reaction or for a Grade 3 dermatologic reaction that does not recover after withholding 1 to 2 doses.

Dilution

Solution may contain a small amount of visible, translucent-to-white, amorphous, and proteinaceous panitumumab particulates (will be removed by in-line filter). Do not use if solution is discolored. Do not shake. Withdraw calculated dose from vial. Dilute to a total volume of 100 mL with NS. Doses higher than 1,000 mg should be diluted to a volume of 150 mL. (Withdraw a volume of NS equal to the volume of the calculated dose from the infusion bag.) Final concentration should not exceed 10 mg/mL. Mix diluted solution by gentle inversion. Do not shake.

Compatibility

Manufacturer states, “Should not be mixed with, or administered as an infusion with, other medicinal products. No other medications should be added to solutions containing panitumumab.”

Rate of administration

Flush line before and after panitumumab administration with NS. Do not administer as an IV push or bolus. Administer with an IV infusion pump using a low–protein binding, 0.2- or 0.22-micron, in-line filter.

A single dose equally distributed over 60 minutes. If the first infusion is tolerated, administer subsequent infusions over 30 to 60 minutes. Doses over 1,000 mg should be administered over 90 minutes. Reduce rate of infusion by 50% in patients experiencing a Grade 1 or 2 infusion reaction.

Actions

A genetically engineered recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). EGFR is a transmembrane glycoprotein that is expressed in many normal epithelial tissues, including skin and hair follicles. Overexpression of EGFR is detected in many human cancers, including those of the colon and rectum. Interaction of EGFR with its normal ligands leads to a series of reactions that regulate the transcription of molecules involved with cellular growth and survival, motility, proliferation, and transformation. Panitumumab binds to EGFR on both normal and tumor cells, inhibiting the binding of normal ligands to EGFR. This competitive binding results in inhibition of cell growth, induction of apoptosis, decreased proinflammatory cytokine and vascular growth factor production, and internalization of EGFR. The end result is inhibition of growth and survival of selected human tumor cells that express EGFR. Half-life is approximately 7.5 days (range 3.6 to 10.9 days).

Indications and uses

Treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use. May be used as first-line therapy in combination with FOLFOX (5-fluorouracil [5-FU], leucovorin, and oxaliplatin [Eloxatin]) or as monotherapy following disease progression after prior treatment with fluoropyrimidine (fluorouracil [5-FU])-, oxaliplatin-, and irinotecan (Camptosar)-containing chemotherapy.

Contraindications

None known. See Precautions.

Precautions

Panitumumab should be used only for treatment of patients with KRAS wild-type mCRC as determined by an FDA-approved test. In studies, patients with KRAS-mutant mCRC tumors receiving panitumumab in combination with FOLFOX experienced some overall survival compared with patients receiving FOLFOX alone. Perform the assessment for KRAS mutational status in colorectal cancer laboratories with demonstrated proficiency in the technology required for testing. ■ Dermatologic toxicities were reported in 90% of patients and were severe (NCI-CTC/CTCAE Grade 3 or higher) in 15% of patients. Manifestations included dermatitis acneiform, dry skin, erythema, paronychia, pruritus, rash, skin exfoliation, and skin fissures. Severe dermatologic toxicities were complicated by infection. Life-threatening and fatal infectious complications, including necrotizing fasciitis, abscesses requiring incision and drainage, and sepsis, have been observed. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been reported. It is unclear whether these reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (e.g., Stevens-Johnson syndrome or toxic epidermal necrolysis). See Dose Adjustments and Antidote. ■ Sunlight may exacerbate dermatologic toxicity. Protection from sun is advised; see Patient Education. ■ Infusion reactions, some severe, have been reported. Fatal reactions have been reported. Administer in a facility with adequate emergency medical equipment and medications for treating these reactions and for responding to any medical emergency; see Rate of Administration and Antidote. ■ Increased mortality and toxicity were seen in studies in which panitumumab was administered in combination with bevacizumab (Avastin) and chemotherapy; see manufacturer’s prescribing information. ■ Electrolyte abnormalities have been reported; see Monitor. ■ Fatal and nonfatal cases of interstitial lung disease (ILD) and pulmonary fibrosis have been reported; see Monitor. In patients with a history of interstitial pneumonitis or pulmonary fibrosis or with evidence of interstitial pneumonitis or pulmonary fibrosis, the benefit of therapy versus the risk of pulmonary complications must be considered. ■ Severe diarrhea and dehydration leading to acute renal failure and other complications have been observed in patients treated with panitumumab in combination with chemotherapy. ■ Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported. ■ A protein substance. Potential for immunogenicity exists. Anti-panitumumab antibodies have been detected in a small number of patients. No evidence of altered safety profiles has been confirmed.

Drug/lab interactions

Formal drug interaction studies have not been conducted.

Side effects

The most commonly reported side effects of panitumumab as monotherapy are diarrhea, fatigue, nausea, paronychia, and skin rash with variable presentations. The most common serious reactions, as well as the reactions that lead most often to discontinuation of therapy, were general physical health deterioration and intestinal obstruction. Side effects occurring in 5% or more of patients receiving panitumumab as monotherapy included acne, acneiform dermatitis, cough, dry skin, dyspnea, erythema, exfoliative rash, mucosal inflammation, nail disorders, rash, skin exfoliation, skin fissures, skin ulcer, stomatitis, and vomiting. The most commonly reported side effects when panitumumab was used in combination with chemotherapy were acneiform dermatitis, anorexia, asthenia, diarrhea, dry skin, hypokalemia, hypomagnesemia, mucosal inflammation, paronychia, pruritus, rash, and stomatitis. The most common serious reactions were diarrhea and dehydration. The most commonly reported side effects leading to discontinuation were acneiform dermatitis, diarrhea, fatigue, hypersensitivity, paresthesia, and rash. Side effects occurring in 5% or more of patients receiving panitumumab in combination with chemotherapy included acne, alopecia, conjunctivitis, dehydration, epistaxis, erythema, nail disorders, palmar-plantar erythrodysesthesia syndrome, skin fissures, and weight decrease. Other serious but less frequently reported side effects as outlined in Precautions included acute renal failure, infusion reactions, interstitial lung disease/pulmonary fibrosis, and ocular toxicity.

Antidote

Notify physician of any side effects; most will be treated symptomatically. Replace electrolytes parenterally or orally as indicated. Reduce infusion rate by 50% if a mild or moderate (Grade 1 or 2) infusion reaction occurs. Discontinue panitumumab for a serious infusion reaction (Grade 3 or 4). Depending on the severity and/or persistence of the reaction, discontinue permanently. Hold or discontinue panitumumab if dermatologic or soft tissue toxicities Grade 3 or higher occur, if they are considered intolerable, or if severe or life-threatening inflammatory or infectious complications occur. See Dose Adjustments for criteria to resume or permanently discontinue treatment. Discontinue if ILD is confirmed. Interrupt or discontinue panitumumab infusion for acute or worsening keratitis. Treat hypersensitivity or infusion reaction as indicated (e.g., oxygen, antihistamines [e.g., diphenhydramine (Benadryl)], epinephrine [Adrenalin], corticosteroids, vasopressors [e.g., dopamine], ventilation equipment, and/or fluids). Resuscitate as necessary.

Usual dose

Given as an alternative to continued oral therapy. Resume oral therapy as soon as practical.

Dose adjustments

No dose adjustments are necessary based on race or gender; in the elderly; in patients with mild, moderate, or severe renal insufficiency; in patients on hemodialysis; or in patients with mild to severe impaired hepatic function. Doses higher than 40 mg/day have not been studied in patients with hepatic impairment.

Dilution

Compatibility (underline indicates conflicting compatibility information)

Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.

Manufacturer states, “Administer through a dedicated line or through a Y-site. Should not be simultaneously administered through the same line with other intravenous solutions.” See Rate of Administration. Manufacturer lists as incompatible at the Y-site with midazolam (Versed) and states, “May not be compatible with products containing zinc.” Discontinue if discoloration or precipitation occurs with any drug at the Y-site.

One source suggests the following compatibilities:

Rate of administration

Flush IV line before and after administration of pantoprazole with compatible infusion solutions (D5W, NS, or LR).

Concentration determines the rate of administration.

Actions

A proton pump inhibitor (PPI) that suppresses the final step in gastric acid production. Acts at the secretory surface of the gastric parietal cell. Inhibits both basal and stimulated gastric acid secretion irrespective of the stimulus. Does not accumulate and pharmacokinetics are not altered with multiple daily dosing. Onset of antisecretory activity is within 15 to 30 minutes. Half-life is approximately 1 hour. However, duration of antisecretory effect persists longer than 24 hours. Distributed mainly in extracellular fluid. Highly bound by serum protein (primarily albumin). Extensively metabolized in the liver through the cytochrome P₄₅₀ system (primarily through CYP2C19 and, to a lesser extent, through CYP3A4). Metabolism is independent of the route of administration (intravenous or oral). Primarily excreted in urine with some excretion in feces. Secreted in breast milk.

Indications and uses

Short-term treatment (7 to 10 days) of gastroesophageal reflux disease (GERD) with a history of erosive esophagitis, as an alternative to oral therapy. ■ Treatment of pathologic hypersecretion associated with Zollinger-Ellison syndrome or other pathologic hypersecretory conditions.

Contraindications

Known hypersensitivity to pantoprazole (Protonix), other substituted benzimidazoles (e.g., esomeprazole [Nexium], omeprazole [Prilosec]), or any component of the formulation.

Precautions

For IV use only; do not give IM or SC. ■ Gastric malignancy may be present even though patient’s symptoms improve with pantoprazole therapy. ■ Formulation contains edetate disodium, which can chelate zinc; see Monitor. ■ Should be discontinued as soon as the patient is able to resume treatment with pantoprazole delayed-release tablets or oral suspension. ■ Data on safe and effective dosing for other conditions (including life-threatening upper GI bleeds) not available. 40 mg IV of pantoprazole daily does not raise gastric pH levels sufficiently to treat such life-threatening conditions. ■ Hypersensitivity reactions, including anaphylaxis and severe skin reactions (e.g., erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), have been reported. ■ May be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. Risk increased in patients receiving high-dose (multiple daily doses) and long-term therapy (a year or longer). Use lowest dose and shortest duration of therapy appropriate for the condition being treated. ■ In patients treated with proton pump inhibitors (PPIs) for at least 3 months and, in most cases, after a year of treatment, hypomagnesemia (symptomatic and asymptomatic) has been reported. Serious adverse events, including arrhythmias, seizures, and tetany, have occurred. Discontinuation of the PPI and magnesium replacement have been required. ■ May be associated with an increased risk of Clostridium difficile–associated diarrhea (CDAD), especially in hospitalized patients. Consider in patients who develop diarrhea that does not improve. ■ Acute interstitial nephritis has been observed and is generally attributed to an idiopathic hypersensitivity reaction. May occur at any time during therapy. Discontinue pantoprazole if it occurs. ■ Use caution in transplant patients receiving mycophenolate mofetil (CellCept). ■ See Drug/Lab Interactions.

Drug/lab interactions

Because of profound and long-lasting inhibition of gastric acid secretion, pantoprazole may interfere with the absorption of drugs in which gastric pH is an important determinant of their bioavailability. Absorption of atazanavir (Reyataz), erlotinib (Tarceva), iron salts (ferrous sulfate), ketoconazole (Nizoral), and mycophenolate mofetil (CellCept) can decrease; other drugs (e.g., digoxin [Lanoxin]) can increase. Coadministration of mycophenolate mofetil (MMF) and omeprazole (Prilosec) in transplant patients receiving MMF reduces the exposure to MMF’s active metabolite, mycophenolic acid; see Precautions. ■ Increases in INR and PT have been reported when administered concurrently with warfarin (Coumadin); monitoring of INR and PT indicated. ■ Concurrent use with atazanavir (Reyataz) or nelfinavir (Viracept) is not recommended. Coadministration of proton pump inhibitors (e.g., esomeprazole [Nexium], pantoprazole [Protonix]) results in a significant reduction in atazanavir or nelfinavir plasma concentrations, thereby inhibiting atazanavir’s therapeutic effect and increasing development of drug resistance. ■ Long-term use may increase the risk of digoxin toxicity secondary to hypomagnesemia. ■ Patients on long-term therapy receiving concomitant diuretic therapy may be at increased risk for hypomagnesemia. ■ Concomitant use of proton pump inhibitors with high-dose methotrexate may elevate and prolong serum levels of methotrexate and/or its metabolite. May lead to methotrexate toxicity; consider withdrawal of pantoprazole. ■ Concomitant administration of pantoprazole and clopidogrel (Plavix) had no clinically significant effect on clopidogrel-induced platelet aggregation. No dose adjustment of clopidogrel is necessary when administered with approved doses of pantoprazole. ■ Studies suggest that with concurrent use the metabolism and serum concentrations of pantoprazole are not significantly altered by other drugs metabolized by the cytochrome P₄₅₀ system (e.g., clarithromycin [Biaxin], diazepam [Valium], diclofenac [Apo-Diclo], metoprolol [Lopressor], midazolam [Versed], naproxen [Aleve], nifedipine [ProCardia XL], phenytoin [Dilantin], piroxicam [Feldene], theophylline). ■ Studies also suggest that concurrent use with pantoprazole has not been found to significantly alter the metabolism and serum concentrations of the above agents as well as other drugs metabolized by a similar process (e.g., carbamazepine [Tegretol], cisapride [Propulsid], oral contraceptives). Concurrent administration should not require dose adjustment of either drug. ■ Amoxicillin, caffeine, digoxin (Lanoxin), ethanol, glyburide (DiaBeta), and metronidazole (Flagyl IV) had no clinically relevant interactions during clinical studies. ■ May cause false-positive urine screening test for tetrahydrocannabinol (THC).

Side effects

The most frequently occurring side effects are abdominal pain, arthralgias, diarrhea, dizziness, flatulence, headache, nausea, and vomiting. Abscess, blurred vision, chest pain, confusion, dyspnea, gastroenteritis, hemorrhage, hyperglycemia, hypokinesia, increased salivation, injection site reactions including thrombophlebitis, pruritus, rash, speech disorder, tinnitus, transient elevations of serum transaminase, urinary tract infection, and vertigo are reported. Numerous other side effects have been associated with oral pantoprazole.

Antidote

Keep physician informed of all side effects. May be treated symptomatically. Discontinue and initiate appropriate treatment if S/S associated with post-marketing reports occur; see Side Effects. Adverse effects from overdose (up to 240 mg/day in healthy subjects) did not occur during clinical trials. Not removed by hemodialysis.

Usual dose

1 to 4 mL (30 to 120 mg) every 3 hours as indicated. Second dose may be given in 10 minutes only when treating extrasystoles.

Pediatric dose

1.5 mg/kg of body weight every 6 hours; see Maternal/Child.

Dose adjustments

See Drug/Lab Interactions.

Dilution

May be given undiluted or may be diluted in an equal amount of SWFI. Usually not added to IV solutions. May be given through Y-tube or three-way stopcock of infusion set.

Compatibility

Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.

Will form a precipitate with LR.

One source suggests the following compatibilities:

Rate of administration

1 mL (30 mg) or fraction thereof over 2 minutes. Rapid IV injection may cause death.

Actions

A nonnarcotic opium alkaloid, it is a direct smooth muscle relaxant and antispasmodic. Relaxation is noted in vascular system and bronchial musculature and in GI, biliary, and urinary tracts. More effective on muscle in spasm, it has an affinity for the smooth muscle of blood vessels. Affects cardiac muscle to depress conduction and increase refractory period. Improved circulation and muscle relaxation decrease pain. Metabolized in the liver and excreted in the urine.

Indications and uses

Vascular spasm associated with an acute myocardial infarction. ■ Peripheral or pulmonary embolism. ■ Peripheral vascular disease and cerebral angiospastic states. ■ Visceral spasm of ureteral, biliary, or GI colic. ■ Angina pectoris.

Contraindications

Complete AV heart block.

Precautions

Rarely used; active therapeutic value is questioned. ■ Rapid IV injection may cause death. ■ IM injection is preferred. ■ Use with caution in glaucoma and impaired liver function. ■ Large doses can depress AV and intraventricular conduction, resulting in arrhythmias.

Drug/lab interactions

May be used with narcotics if the relaxant effect is not adequate to relieve discomfort. Narcotic dosage should be reduced. ■ Antagonizes effects of levodopa.

Side effects

Blurred or double vision, diaphoresis, discomfort (generalized), flushing, hypertension (slight), hypotension, respiratory depth increase, scleral jaundice, sedation, tachycardia.

Antidote

Notify the physician of any minor side effects. If minor symptoms progress or any major side effect appears, discontinue the drug immediately and notify the physician. Treatment of toxicity will be symptomatic and supportive. Consider diazepam (Valium) or phenytoin (Dilantin) for convulsions. Anesthesia with thiopental and paralysis with a neuromuscular blocking agent may be required. Use dopamine for hypotension. Calcium gluconate may reduce toxic cardiovascular effects. Monitor ECG. Resuscitate as necessary.

Usual dose

The currently accepted target range for intact parathyroid hormone (iPTH) in chronic kidney disease (CKD) Stage 5 patients is no more than 1.5 to 3 times the nonuremic upper limit of normal.

Recommended initial dose is 0.04 to 0.1 mcg/kg administered no more frequently than every other day at any time during dialysis. Doses as high as 0.24 mcg/kg have been safely administered.

Information supplied by the manufacturer suggests that the relative dosing of paricalcitol to calcitriol is 4:1. When converting a patient from calcitriol to paricalcitol, the initial dose of paricalcitol should be four times greater than the patient’s dose of calcitriol.

Pediatric dose

Dose recommendations are based on severity of disease in addition to body weight. A dose is administered at any time during dialysis.

Dose adjustments

Adults:

Adjust dosing based on patient response. If a satisfactory response is not observed, dose may be increased by 2 to 4 mcg at 2- to 4-week intervals. Monitor serum calcium, phosphorus, and calcium × phosphorus product (Ca × P) frequently during any dose adjustment period. See Monitor.

Pediatric patients:

Adjust dose in 0.04-mcg/kg increments based on the levels of serum iPTH, calcium, and Ca × P (from clinical trials).

Adults and pediatric patients:

Reduce dose or interrupt therapy if elevated calcium level or a Ca × P product of greater than 75 is noted. Reinitiate therapy at a lower dose when parameters have normalized. ■ Paricalcitol dose may need to be reduced as parathyroid hormone (PTH) levels decrease in response to therapy. The currently accepted target range for intact parathyroid hormone (iPTH) in patients with chronic kidney disease (CKD) is no more than 1.5 to 3 times the nonuremic upper limit of normal. Incremental dosing must be individualized and commensurate with PTH, serum calcium, and phosphorus levels. The following chart is a suggested approach to dose titration.

Paricalcitol Suggested Dosing Guidelines
PTH Level	Paricalcitol Dose
The same or increasing	Increase
Decreasing by <30%	Increase
Decreasing by >30%, <60%	Maintain
Decreasing by >60%	Decrease
11/2 to 3 times the upper limit of normal	Maintain

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