Sunday, May 30, 2010

Alosetron

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Lotronex® may be confused with Lovenox®, Protonix®

International issues:
Lotronex® may be confused with Lotanax® which is a brand name for terfenadine in the Czech Republic

MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088624.pdf, must be dispensed with this medication for each new outpatient prescription and refill.

U.S. BRAND NAMES — Lotronex®

PHARMACOLOGIC CATEGORY
Selective 5-HT3 Receptor Antagonist

DOSING: ADULTS — IBS: Female: Oral: Initial: 0.5 mg twice daily for 4 weeks, with or without food; if tolerated, but response is inadequate, may be increased after 4 weeks to 1 mg twice daily. If response is inadequate after 4 weeks of 1 mg twice-daily dosing, discontinue treatment.
Note: Discontinue immediately if constipation or signs/symptoms of ischemic colitis occur. Do not reinitiate in patients who develop ischemic colitis.

DOSING: ELDERLY — Refer to adult dosing. Dosage adjustment is not required; however, postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation.

DOSING: RENAL IMPAIRMENT — The need for dosage adjustment has not been defined (due to limited information on activity of metabolites).

DOSING: HEPATIC IMPAIRMENT — In mild-to-moderate dysfunction (Child-Pugh score ≤ 9), use caution. Contraindicated in severe hepatic dysfunction (Child-Pugh score ≥ 10).

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:
Lotronex®: 0.5 mg, 1 mg

DOSAGE FORMS: CONCISE
Tablet:
Lotronex®: 0.5 mg, 1 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — May be administered with or without food; however, when administered with food, absorption may be reduced by approximately 25%.

USE — Treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have failed to respond to conventional therapy

ADVERSE REACTIONS SIGNIFICANT
>10%: Gastrointestinal: Constipation (dose related; 29%)

2% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (5%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)

≤ 1% (Limited to important or life-threatening): Allergic skin reactions, alopecia, anxiety, arrhythmia, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, dermatitis, diaphoresis, diverticulitis, dyspepsia, extrasystoles, fatigue, fluid disturbances, gastroenteritis, GI impaction, GI intussusception, GI lesions, GI motility decreased, GI obstructions, GI perforation, GI spasms, GI ulceration, headache, hematoma, hemorrhage, hepatitis, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, ischemic colitis, memory effects, muscle pain/stiffness, occult stools, pain, proctitis, rash, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, small bowel mesenteric ischemia, tachyarrhythmia, temperature regulation impairment, tremor, ulcerative colitis, urinary frequency, urticaria

CONTRAINDICATIONS — Do not start treatment in patients who are constipated. Hypersensitivity to alosetron or any component of the formulation; history of severe or chronic constipation or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; diverticulitis, current or history of Crohn's disease, or ulcerative colitis; severe hepatic impairment; history of impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; patients unable to understand or comply with "Patient-Physician" agreement; concomitant administration with fluvoxamine

WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below. Constipation: See "Concerns related to adverse effects" below. Ischemic colitis: See "Concerns related to adverse effects" below. Patient-Physician agreement: See "Other warnings/precautions" below.

Concerns related to adverse effects: Constipation: [U.S. Boxed Warning]: Discontinue immediately in patients who develop constipation; serious complications of constipation have been infrequently reported (obstruction, ileus, perforation, impaction, toxic megacolon, secondary ischemia). Constipation is a frequent, dose-related side effect; risk for complications from constipation may be increased in elderly, debilitated patients, or with concurrent use of other medications which decrease GI motility. Nonsevere constipation may be managed by temporarily interrupting therapy. Do not initiate in patients with constipation. Do not initiate in patients with constipation. Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue and evaluate immediately in patients who experience rectal bleeding or a sudden worsening of abdominal pain, and do not restart therapy if ischemic colitis is diagnosed.

Disease-related concerns: Hepatic impairment: Use caution in mild-to-moderate hepatic impairment (Child-Pugh score ≤ 9); contraindicated in severe impairment (Child-Pugh score ≥ 10).

Special populations: Elderly: Use with caution in the elderly due to increased risk of complications from constipation. Males: Safety and efficacy have not been established in males. Pediatrics: Safety and efficacy have not been established in children.

Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome with inadequate response to conventional therapy. Patient-Physician agreement: [U.S. Boxed Warning]: Should only be prescribed by physicians enrolled in the Prometheus' Prescribing Program for Lotronex®. Patients must read and sign a "Patient-Physician" agreement before receiving the initial prescription.

RESTRICTIONS — Only physicians enrolled in Prometheus' Prescribing Program for Lotronex® may prescribe this medication. Program stickers must be affixed to all prescriptions; no phone, fax, or computerized prescriptions are permitted with this program.

METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)

DRUG INTERACTIONS
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy

CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy

Fluvoxamine: May decrease the metabolism of Alosetron. Risk X: Avoid combination

Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with food, absorption may be reduced by ~25%.

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Alosetron should be used in pregnant women only if clearly needed.

LACTATION — Excretion in breast milk unknown/use caution

BREAST-FEEDING CONSIDERATIONS — Animal studies indicate that alosetron and/or metabolites are excreted in breast milk. It is not known if alosetron in excreted in human milk. Caution should be used in administering alosetron to a nursing woman.

DIETARY CONSIDERATIONS — May be taken with or without food.

PRICING — (data from drugstore.com)
Tablets (Lotronex)
1 mg (30): $428.32

MECHANISM OF ACTION — Alosetron is a potent and selective antagonist of a subtype of the serotonin 5-HT3 receptor. 5-HT3 receptors are ligand-gated ion channels extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions. In patients with irritable bowel syndrome, blockade of these channels may reduce pain, abdominal discomfort, urgency, and diarrhea.

PHARMACODYNAMICS / KINETICS
Distribution: Vd: 65-95 L

Protein binding: 82%

Metabolism: Extensive hepatic metabolism. Alosetron is metabolized by CYP2C9, 3A4, and 1A2. Thirteen metabolites have been detected in the urine. Biological activity of these metabolites in unknown.

Bioavailability: Mean: 50% to 60% (range: 30% to >90%); decreased with food (25%)

Half-life elimination: 1.5 hours for alosetron

Time to peak: 1 hour after oral administration

Excretion: Urine (73%) and feces (24%); 7% as unchanged drug (1% feces, 6% urine)

PATIENT INFORMATION — Take with or without food. Do not take if you are frequently constipated; constipation is a side effect associated with this medication and can lead to serious complications. Stop taking this medication and call your prescriber if you become constipated, or if you have sudden worsening of abdominal pain, severe constipation, or blood in your stool. Do not continue taking the medication until you have spoken with your prescriber; if after stopping the medication, constipation does not resolve, call your prescriber again. Notify your prescriber if you are pregnant, plan on becoming pregnant, or if you are breast-feeding.

Almotriptan

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Axert® may be confused with Antivert®

U.S. BRAND NAMES — Axert®

PHARMACOLOGIC CATEGORY
Antimigraine Agent
Serotonin 5-HT1B, 1D Receptor Agonist

DOSING: ADULTS — Migraine: Oral: Initial: 6.25-12.5 mg in a single dose; if the headache returns, repeat the dose after 2 hours; no more than 2 doses (maximum daily dose: 25 mg)

Note: The safety of treating more than 4 migraines/month has not been established.

Dosage adjustment with concomitant use of an enzyme inhibitor:
Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use

DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg

DOSING: HEPATIC IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, as malate:
Axert®: 6.25 mg, 12.5 mg

DOSAGE FORMS: CONCISE
Tablet:
Axert®: 6.25 mg, 12.5 mg

GENERIC EQUIVALENT AVAILABLE — No

USE — Acute treatment of migraine with or without aura in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥ 4 hours when left untreated)

ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Somnolence (≤ 5%), dizziness (≤ 4%), headache (≤ 2%)
Gastrointestinal: Nausea (1% to 3%), vomiting (≤ 2%), xerostomia (1%)
Neuromuscular & skeletal: Paresthesia (≤ 1%)

<1% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo

CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses. Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration. Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions following 5-HT1 agonist administration in patients with and without a history of hypertension. Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT1 agonist administration. Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.

Disease-related concerns: Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is "satisfactory," the first dose of almotriptan should be given in the healthcare provider's office. All patients should undergo periodic evaluation of cardiovascular status during treatment. Hepatic impairment: Use with caution in patients with hepatic impairment. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended. Renal impairment: Use with caution in patients with moderate-to-severe renal failure. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.

Concurrent drug therapy issues: Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce almotriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.

Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age. Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).

Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.

METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4

DRUG INTERACTIONS
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification

Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination

MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification

Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use in pregnancy should be limited to situations where benefit outweighs risk to fetus. In some (but not all) animal studies, administration was associated with embryolethality, fetal malformations, and decreased pup weight.

LACTATION — Excretion in breast milk unknown/use caution

DIETARY CONSIDERATIONS — May be taken without regard to meals

PRICING — (data from drugstore.com)
Tablets (Axert)
6.25 mg (6): $130.08
12.5 mg (12): $238.94

CANADIAN BRAND NAMES — Axert®

INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)

MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine

PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed

Distribution: Vd: ~180-200 L

Protein binding: ~35%

Metabolism: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites

Bioavailability: ~70%

Half-life elimination: 3-4 hours

Time to peak, plasma: 1-3 hours

Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)

PATIENT INFORMATION — This drug is to be used to reduce your migraine not to prevent or reduce the number of attacks. Take exactly as directed. If headache returns or is not fully resolved, the dose may be repeated after 2 hours. Do not use more than two doses in 24 hours. Do not take within 24 hours of other migraine medication without consulting prescriber. You may experience dizziness, fatigue, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report immediately chest pain, palpitations, feeling of tightness or pressure in chest, jaw, or throat; acute headache or dizziness; muscle cramping, pain, or tremors; skin rash; hallucinations, anxiety, panic; or other adverse reactions.

Allopurinol MEDICATION SAFETY ISSUES Sound-alike/look-alike issues:   Allopurinol may be confused with Apresoline   Zyloprim® may be confused with X

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Allopurinol may be confused with Apresoline
Zyloprim® may be confused with Xylo-Pfan®, ZORprin®, Zovirax®

U.S. BRAND NAMES — Aloprim™ ; Zyloprim®

PHARMACOLOGIC CATEGORY
Xanthine Oxidase Inhibitor

DOSING: ADULTS — Doses >300 mg should be given in divided doses.

Gout: Oral: Mild: 200-300 mg/day; Severe: 400-600 mg/day; to reduce the possibility of acute gouty attacks, initiate dose at 100 mg/day and increase weekly to recommended dosage. Maximum daily dose: 800 mg/day.

Secondary hyperuricemia associated with chemotherapy:
Oral: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy
I.V.: 200-400 mg/m2/day (maximum: 600 mg/day)
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.

Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses

DOSING: PEDIATRIC

(For additional information see "Allopurinol: Pediatric drug information")
Gout: Children >10 years: Refer to adult dosing.

Recurrent calcium oxalate stones: Children >10 years: Refer to adult dosing.

Secondary hyperuricemia associated with chemotherapy:
Oral: Children ≤ 10 years: 10 mg/kg/day in 2-3 divided doses or 200-300 mg/m2/day in 2-4 divided doses, maximum: 800 mg/24 hours, for prevention of acute uric acid nephropathy (begin 1-2 days before chemotherapy)
Alternative (manufacturer labeling):
<6 years: 150 mg/day in 3 divided doses
6-10 years: 300 mg/day in 2-3 divided doses
>10 years: Refer to adult dosing.
I.V.:
Children ≤ 10 years: Starting dose: 200 mg/m2/day
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. Adequate fluid intake and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Children >10 years: Refer to adult dosing.

DOSING: ELDERLY — Oral: Initial: 100 mg/day; increase until desired uric acid level is obtained. Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Oral: Must be adjusted due to accumulation of allopurinol and metabolites;

Adult Maintenance Doses of Allopurinol

Note: Doses are based on a standard maintenance dose of 300 mg of allopurinol per day for a patient with a creatinine clearance of 100 mL/minute. Clcr 140 mL/minute: 400 mg daily Clcr 120 mL/minute: 350 mg daily Clcr 100 mL/minute: 300 mg daily Clcr 80 mL/minute: 250 mg daily Clcr 60 mL/minute: 200 mg daily Clcr 40 mL/minute: 150 mg daily Clcr 20 mL/minute: 100 mg daily Clcr 10 mL/minute: 100 mg every 2 days Clcr 0 mL/minute: 100 mg every 3 days

I.V.:
Clcr 10-20 mL/minute: Administer 200 mg/day.
Clcr 3-10 mL/minute: Administer 100 mg/day.
Clcr <3 mL/minute: Administer 100 mg/day at extended intervals.

Hemodialysis: Administer dose after hemodialysis or administer 50% supplemental dose.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution, as sodium: 500 mg
Aloprim™ : 500 mg

Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Aloprim™ : 500 mg

Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION
Oral: Should administer oral forms after meals with plenty of fluid.

I.V.: Infuse over 15-60 minutes. The rate of infusion depends on the volume of the infusion. Whenever possible, therapy should be initiated at 24-48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). I.V. daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.

COMPATIBILITY — Stable in D5W, NS, sterile water for injection.

Y-site administration: Compatible: Acyclovir, aminophylline, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, cefazolin, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cisplatin, co-trimoxazole, cyclophosphamide, dactinomycin, dexamethasone sodium phosphate, doxorubicin liposome, enalaprilat, etoposide, famotidine, fluconazole, fludarabine, fluorouracil, furosemide, ganciclovir, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, lorazepam, mannitol, mesna, methotrexate, metronidazole, mitoxantrone, morphine, piperacillin, plicamycin, potassium chloride, ranitidine, thiotepa, ticarcillin, ticarcillin/clavulanate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem/cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine edisylate, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine.

USE
Oral: Prevention of attack of gouty arthritis and nephropathy; treatment of secondary hyperuricemia which may occur during treatment of tumors or leukemia; prevention of recurrent calcium oxalate calculi

I.V.: Treatment of elevated serum and urinary uric acid levels when oral therapy is not tolerated in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer chemotherapy

ADVERSE REACTIONS SIGNIFICANT
Dermatologic: Rash

Endocrine & metabolic: Gout (acute)

Gastrointestinal: Diarrhea, nausea

Hepatic: Alkaline phosphatase increased, liver enzymes increased

<1% (Limited to important or life-threatening): Abdominal pain, agranulocytosis, alopecia, angioedema, aplastic anemia, arthralgia, bronchospasm, cataracts, cholestatic jaundice, dermatitis (eczematoid, exfoliative, vascular bullous), dyspepsia, ecchymosis, eosinophilia, epistaxis, fever, gastritis, granuloma annulare, hepatitis, gynecomastia, headache, hepatic necrosis, hepatomegaly, hyperbilirubinemia, hypersensitivity reactions, leukocytosis, leukopenia, lichen planus, loss of taste perception, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, paresthesia, purpura, pruritus, renal failure, somnolence, Stevens-Johnson syndrome, taste perversion, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vomiting

CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Allergic reaction: Has been associated with a number of hypersensitivity reactions, including severe reactions (vasculitis and Stevens-Johnson syndrome); discontinue at first sign of rash. Bone marrow suppression: Has been reported; use caution with other drugs causing myelosuppression. Hepatotoxicity: Reversible hepatotoxicity has been reported; use with caution in patients with pre-existing hepatic impairment.

Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; may be at increased risk for hypersensitivity reactions. Dosage adjustments needed.

Concurrent drug therapy issues: ACE inhibitors: The risk of hypersensitivity may be increased in patients receiving ACE inhibitors. Amoxicillin/ampicillin: Risk of skin rash may be increased in patients receiving amoxicillin or ampicillin. Azathioprine/mercaptopurine: Use with caution in patients taking mercaptopurine or azathioprine; dosage adjustment necessary. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.

DRUG INTERACTIONS
ACE Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification

Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy

Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy

Antacids: May decrease the absorption of Allopurinol. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification

AzaTHIOprine: Allopurinol may decrease the metabolism of AzaTHIOprine. Risk D: Consider therapy modification

CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

ChlorproPAMIDE: Allopurinol may increase the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy

Cyclophosphamide: Allopurinol may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, bone marrow suppression. Risk C: Monitor therapy

Didanosine: Allopurinol may increase the serum concentration of Didanosine. Risk X: Avoid combination

Loop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy

Mercaptopurine: Allopurinol may decrease the metabolism of Mercaptopurine. Risk D: Consider therapy modification

Pivampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Pivampicillin. Risk C: Monitor therapy

Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy

Thiazide Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: May decrease effectiveness.

Iron supplements: Hepatic iron uptake may be increased.

Vitamin C: Large amounts of vitamin C may acidify urine and increase kidney stone formation.

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — There are few reports describing the use of allopurinol during pregnancy; no adverse fetal outcomes attributable to allopurinol have been reported in humans; use only if potential benefit outweighs the potential risk to the fetus.

LACTATION — Enters breast milk/use caution (AAP rates "compatible")

DIETARY CONSIDERATIONS — Should administer oral forms after meals with plenty of fluid. Fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).

PRICING — (data from drugstore.com)
Tablets (Zyloprim)
100 mg (30): $23.99
300 mg (30): $56.04

MONITORING PARAMETERS — CBC, serum uric acid levels, I & O, hepatic and renal function, especially at start of therapy

REFERENCE RANGE — Uric acid, serum: An increase occurs during childhood

Adults:
Male: 3.4-7 mg/dL or slightly more
Female: 2.4-6 mg/dL or slightly more

Values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.

CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®

INTERNATIONAL BRAND NAMES — Adenock (JP); AL (PH); Alinol (TH); Allo (CO); Allo 300 (DE); Allo-Puren (DE); Allobeta (AU); Allohexal (AU); Allopin (TH); Allopur (CH, NO); Allopurinol (PL); Allopurinol-ratiopharm (LU); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allpargin (LU); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (BB, BM, BS, BZ, GY, JM, NL, PR, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpuric (LU); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (PL); Aprinol (JP); Apurin (FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB); Capurate (TW); Cellidrin (DE); Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Etindrax (MX); Foligan (DE); Genozyl (MX); Gichtex (AT); Hamarin (GB); Hexanurat (DK); Huma-Purol (HU); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (PH); Masaton (JP); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Milurit (BG, HK, HN, HU, PL); Miniplanor (JP); Neufan (JP); Nilapur (ID); Nipurol (VE); No-Uric (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Pritanol (ID); Progout (AU, HK, SG); Proxuric (ID); Puribel 300 (MX); Puricemia (ID); Puricos (ZA); Purinol (MY); Puristen (PH); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Trianol (PH); Unizuric 300 (MX); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, PR, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZA, ZM, ZW); Urosin (AT, DE, EC, LU); Xandase (TH); Xanturic (FR); Xanurace (PH); Zylapour (GR); Zyloprim (AU, BB, BM, BS, BZ, CR, DO, GY, JM, MX, NI, NL, PA, PH, PY, SR, SV, TT); Zyloric (AE, AT, BE, BF, BG, BH, BJ, BR, CH, CI, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HN, ID, IE, IL, IN, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TN, TR, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Zyroric (KP)

MECHANISM OF ACTION — Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.

PHARMACODYNAMICS / KINETICS
Onset of action: Peak effect: 1-2 weeks

Absorption: Oral: ~80%; Rectal: Poor and erratic

Distribution: Vd: ~1.6 L/kg; Vss: 0.84-0.87 L/kg; enters breast milk

Protein binding: <1%

Metabolism: ~75% to active metabolites, chiefly oxypurinol

Bioavailability: 49% to 53%

Half-life elimination:
Normal renal function: Parent drug: 1-3 hours; Oxypurinol: 18-30 hours
End-stage renal disease: Prolonged

Time to peak, plasma: Oral: 30-120 minutes

Excretion: Urine (76% as oxypurinol, 12% as unchanged drug)

Allopurinol and oxypurinol are dialyzable

PATIENT INFORMATION — Take after meals with plenty of fluid (at least 10-12 glasses of fluids per day); discontinue the drug and contact prescriber at first sign of rash, painful urination, blood in urine, irritation of the eyes, or swelling of the lips or mouth; may cause drowsiness; alcohol decreases effectiveness

Alitretinoin

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Panretin® may be confused with pancreatin

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

U.S. BRAND NAMES — Panretin®

PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Retinoic Acid Derivative

DOSING: ADULTS
Kaposi's sarcoma: Topical: Apply gel twice daily to cutaneous lesions.

T-cell lymphomas (unlabeled use): Topical: Apply gel twice daily to cutaneous lesions.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Gel:
Panretin®: 0.1% (60 g)

DOSAGE FORMS: CONCISE
Gel:
Panretin®: 0.1% (60 g)

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Do not use occlusive dressings.

USE — Orphan drug: Topical treatment of cutaneous lesions in AIDS-related Kaposi's sarcoma

USE - UNLABELED / INVESTIGATIONAL — Cutaneous T-cell lymphomas

ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Pain (0% to 34%)
Dermatologic: Rash (25% to 77%), pruritus (8% to 11%)
Neuromuscular & skeletal: Paresthesia (3% to 22%)

5% to 10%:
Cardiovascular: Edema (3% to 8%)
Dermatologic: Exfoliative dermatitis (3% to 9%), skin disorder (0% to 8%)

CONTRAINDICATIONS — Hypersensitivity to alitretinoin, other retinoids, or any component of the formulation; pregnancy

WARNINGS / PRECAUTIONS
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.

Concerns related to adverse effects: Photosensitivity: May be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.

Concurrent drug therapy issues: Products containing DEET: Do not use concurrently with topical products containing DEET.

Special populations: Elderly: Safety has not been established in the elderly. Pediatrics: Safety has not been established in children. Pregnancy: May cause fetal harm if absorbed by a woman who is pregnant.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — D (show table)

PREGNANCY IMPLICATIONS — Potentially teratogenic and/or embryotoxic; limb, craniofacial, or skeletal defects have been observed in animal models. If used during pregnancy or if the patient becomes pregnant while using alitretinoin, the woman should be advised of potential harm to the fetus. Women of childbearing potential should avoid becoming pregnant.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — Excretion in human breast milk is unknown; women are advised to discontinue breast-feeding prior to using this medication.

CANADIAN BRAND NAMES — Panretin®

INTERNATIONAL BRAND NAMES — Panretin (AR, AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IT, NL, NO, PT, RU, SE, TR)

MECHANISM OF ACTION — Binds to retinoid receptors to inhibit growth of Kaposi's sarcoma

PHARMACODYNAMICS / KINETICS — Absorption: Not extensive

PATIENT INFORMATION — For external use only; avoid UV light exposure (sun or sunlamps) of treated areas; avoid DEET-containing products

Aliskiren and hydrochlorothiazide

U.S. BRAND NAMES — Tekturna HCT®

PHARMACOLOGIC CATEGORY
Diuretic, Thiazide
Renin Inhibitor

DOSING: ADULTS — Hypertension: Oral: One tablet daily; dosage must be individualized (see below). May be substituted for previously titrated dosages of the individual components. Titrate at 2- to 4-week intervals as necessary.

Patients not controlled with single-agent therapy: Initiate by adding the lowest available dose of the alternative component (aliskiren 150 mg or hydrochlorothiazide 12.5 mg); titrate to effect (maximum daily aliskiren dose: 300 mg; maximum daily hydrochlorothiazide dose: 25 mg)

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — Not recommended in patients with Clcr <30 mL/minute

DOSING: HEPATIC IMPAIRMENT — Dosage adjustment not required.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:
Tekturna HCT®:
150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg
150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg
300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg
300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg

DOSAGE FORMS: CONCISE
Tablet:
Tekturna HCT®: 150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg; 150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg; 300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg; 300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Administer with or without meals.

USE — Treatment of hypertension (not recommended for initial treatment)

ADVERSE REACTIONS SIGNIFICANT — Frequencies reported with combination product. See individual monographs for additional adverse effects reported with each agent.

>10%: Renal: BUN increased (12%)

1% to 10%:
Central nervous system: Dizziness (2%), vertigo (1%)
Endocrine & metabolic: Hypokalemia (2%), uric acid level increased (2%)
Gastrointestinal: Diarrhea (2%)
Hepatic: ALT increased (1%)
Neuromuscular & skeletal: Arthralgia (1%), weakness (1%)
Respiratory: Cough (1%)
Miscellaneous: Flu-like syndrome (2%)

<1% (Limited to important or life-threatening): Hematocrit decreased, hemoglobin decreased, hyperkalemia

Note: Angioedema and periorbital edema have been reported with aliskiren. Severe dermatologic reactions and pancreatitis have been reported with hydrochlorothiazide.

CONTRAINDICATIONS — Hypersensitivity to hydrochlorothiazide, thiazides, or sulfonamide-derived drugs; anuria

WARNINGS / PRECAUTIONS
Boxed warnings: Pregnancy: See "Special populations" below.

Concerns related to adverse effects: Angioedema: Since the effect of aliskiren on bradykinin levels is unknown, the risk of kinin-mediated etiologies of angioedema occurring is also unknown. Use caution in any patient with a history of angioedema (of any etiology) as angioedema has been observed (rarely) with aliskiren use. Discontinue immediately following any signs and symptoms of angioedema. Electrolyte disturbances: Hyperkalemia may occur with renin inhibitors; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia. Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma. Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in volume- or salt-depleted patients. Photosensitivity: Due to the hydrochlorothiazide component photosensitization may occur. Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure); deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.

Disease-related concerns: Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis. Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. Hepatic impairment: Use caution in patients with hepatic impairment. Avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides. Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Renal artery stenosis: There has been no experience in treating patients with renal artery stenosis; use aliskiren with caution in patients with unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. Renal impairment: Use with caution in patients with renal impairment; not recommended in patients with severe renal impairment (Clcr <30 mL/minute). Avoid hydrochlorothiazide in severe renal disease (ineffective); may precipitate azotemia; discontinue or consider withholding if renal impairment occurs. Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.

Concurrent drug therapy: High potential for interactions: use caution in patients taking strong inhibitors of P-glycoprotein (eg, cyclosporine); concomitant therapy with cyclosporine is not recommended.

Special populations: Pediatrics: Safety and efficacy have not been established in children. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.

METABOLISM / TRANSPORT EFFECTS — See individual agents.

DRUG INTERACTIONS
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy

Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy

Atorvastatin: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy

Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification

Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy

Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy

CycloSPORINE: May increase the serum concentration of Aliskiren. Risk X: Avoid combination

Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination

Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Ketoconazole: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy

Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification

MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification

Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

PREGNANCY RISK FACTOR — D (show table)

PREGNANCY IMPLICATIONS — See individual agents.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — See individual agents.

DIETARY CONSIDERATIONS — Take with or without meals; a high-fat meal reduces aliskiren absorption substantially.

PRICING — (data from drugstore.com)
Tablets (Tekturna HCT)
300-25 mg (30): $102.72

MONITORING PARAMETERS — Blood pressure; serum electrolytes, BUN, serum creatinine; fluid status

MECHANISM OF ACTION — Aliskiren is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.

PHARMACODYNAMICS / KINETICS — See individual agents.

Aliskiren

MEDICATION SAFETY ISSUES
International issues:
Aliskiren may be confused with Aliseum which is a brand name for diazepam in Italy

U.S. BRAND NAMES — Tekturna®

PHARMACOLOGIC CATEGORY
Renin Inhibitor

DOSING: ADULTS — Hypertension: Initial: 150 mg once daily; may increase to 300 mg once daily (maximum: 300 mg/day). Note: Prior to initiation, correct hypovolemia and/or closely monitor volume status in patients on concurrent diuretics during treatment initiation.

DOSING: PEDIATRIC — Children <18 years: Dosage not established.

DOSING: ELDERLY — Refer to adult dosing. No initial dosage adjustment required.

DOSING: RENAL IMPAIRMENT
Mild-to-moderate impairment [GFR >30 mL/minute and/or Scr <1.7 mg/dL (women); Scr <2 mg/dL (men)]: No dose adjustment required

Severe impairment [GFR<30>1.7 mg/dL (women); Scr >2 mg/dL (men)]: Use caution; not studied in severe renal impairment

DOSING: HEPATIC IMPAIRMENT — No dosage adjustment required.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:
Tekturna®: 150 mg, 300 mg

DOSAGE FORMS: CONCISE
Tablet:
Tekturna®: 150 mg, 300 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Administer at the same time daily; may take with or without a meal, but consistent administration with regards to meals is recommended. Avoid taking with high-fat meals.

USE — Treatment of hypertension, alone or in combination with other antihypertensive agents

USE - UNLABELED / INVESTIGATIONAL — Treatment of persistent proteinuria in patients with type 2 diabetes mellitus, hypertension, and nephropathy despite administration of optimized recommended renoprotective therapy (eg, angiotensin II receptor blocker)

ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Dizziness (2%)
Dermatologic: Rash (1%)
Endocrine & metabolic: Hyperkalemia (monotherapy ≤ 1%; concurrent with ACE inhibitor in patients with diabetes 6%)
Gastrointestinal: Diarrhea (1% to 2%)
Hematologic: Creatine kinase increased (>300%: 1%)
Renal: BUN increased (≤ 7%), serum creatinine increased (≤ 7%)
Respiratory: Cough (1%)

<1% (Limited to important or life-threatening): Abdominal pain, anemia, angina, angioedema, dyspepsia, gastroesophageal reflux, gout, hypotension (severe), myositis, renal stone formation, rhabdomyolysis, seizure, uric acid increased

CONTRAINDICATIONS
U.S. labeling: There are no contraindications listed in manufacturer's labeling.

Canada labeling: Hypersensitivity to aliskiren or any component of the formulation

WARNINGS / PRECAUTIONS
Boxed warnings: Pregnancy: See "Special populations" below.

Concerns related to adverse effects: Angioedema: Since the effect of aliskiren on bradykinin levels is unknown, the risk of kinin-mediated etiologies of angioedema occurring is also unknown. Use caution in any patient with a history of angioedema (of any etiology) as angioedema has been observed (rarely) with aliskiren use. Discontinue immediately following any signs and symptoms of angioedema. Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Aggressive early and appropriate management is critical. Hyperkalemia: May occur (rarely) during monotherapy; risk may increase in patients with predisposing factors (eg, renal dysfunction, diabetes mellitus or concomitant use with ACE inhibitors, potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts). Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in patients with an activated renin-angiotensin system (ie, volume or salt-depleted patients)

Disease-related concerns: Renal impairment: Use with caution in patients with severe renal impairment; not studied in patients with severe renal impairment [GFR <30>1.7 mg/dL (women); Scr >2 mg/dL (men)], history of dialysis, nephrotic syndrome, or renovascular hypertension. Use with caution or avoid in patients with deteriorating renal function or renal artery stenosis (bilateral or unilateral).

Concurrent drug therapy issues: High potential for interactions: Use caution in patients taking strong inhibitors of P-glycoprotein (eg, cyclosporine).

Special populations: Pediatrics: Safety and efficacy have not been established in children. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.

METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (minor)

DRUG INTERACTIONS
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy

Atorvastatin: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy

CycloSPORINE: May increase the serum concentration of Aliskiren. Risk X: Avoid combination

Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Ketoconazole: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy

MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic effect of Antihypertensives. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification

Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Food: High-fat meals decrease absorption.

PREGNANCY RISK FACTOR — C (show table) (1st trimester); D (2nd and 3rd trimesters)

PREGNANCY IMPLICATIONS — Medications which act on the renin-angiotensin system are reported to have the following fetal/neonatal effects: Hypotension, neonatal skull hypoplasia, anuria, renal failure, and death; oligohydramnios is also reported. These effects are reported to occur with exposure during the second and third trimesters. There are no adequate and well-controlled studies in pregnant women. [U.S. Boxed Warning]: Based on human data, drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.

LACTATION — Excretion in breast milk unknown/not recommended

DIETARY CONSIDERATIONS — May be taken with or without food; however, a high-fat meal reduces absorption

PRICING — (data from drugstore.com)
Tablets (Tekturna)
150 mg (30): $82.38
300 mg (30): $101.80

MONITORING PARAMETERS — Blood pressure; serum potassium, BUN, serum creatinine

CANADIAN BRAND NAMES — Rasilez®

INTERNATIONAL BRAND NAMES — Enviage (EE); Rasilez (BE, CH, CZ, DE, DK, EE, GB, ID, IE, IL, NO, PE, PH, SE); Tekturna (EE)

MECHANISM OF ACTION — Aliskerin is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Ang II also functions within the Renin-Angiotensin-Aldosterone System (RAAS) as a negative inhibitory feedback mediator within the renal parenchyma to suppress the further release of renin. Thus, reductions in Ang II levels suppress this feedback loop, leading to further increased plasma renin concentrations (PRC) and subsequent activity (PRA). This disinhibition effect can be potentially problematic for ACE inhibitor and ARB therapy, as increased PRA could partially overcome the pharmacologic inhibition of the RAAS. As aliskiren is a direct inhibitor of renin activity, blunting of PRA despite the increased PRC (from loss of the negative feedback) may be clinically advantageous. The effect of aliskiren on bradykinin levels is unknown.

PHARMACODYNAMICS / KINETICS
Onset of action: Maximum antihypertensive effect: Within 2 weeks

Absorption: Poor; absorption decreased by high-fat meal. Aliskiren is a substrate of P-glycoprotein; concurrent use of P-glycoprotein inhibitors may increase absorption.

Metabolism: Extent of metabolism unknown; in vitro studies indicate metabolism via CYP3A4

Bioavailability: ~3%

Half-life elimination: ~24 hours (range: 16-32 hours)

Time to peak, plasma: 1-3 hours

Excretion: Urine (~25% of absorbed dose excreted unchanged in urine); feces (unchanged via biliary excretion)

Alglucosidase alfa

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Alglucosidase alfa may be confused with agalsidase alfa, agalsidase beta, alglucerase

SPECIAL ALERTS
Myozyme® Shortage - January 2009

Inventory levels of Myozyme® (alglucosidase alfa) are low because of increased global demand. Increased production is planned once regulatory agencies throughout the world approve a larger scale manufacturing process. In the U.S., the Food and Drug Administration (FDA) is expected to respond by the end of February. In the meantime, recommended guidelines have been developed to help with clinical decisions during this temporary period of supply constraint. Pediatric dosing regimens will be maintained. However, to continue providing therapy to adult patients, adult regimens will be adjusted by increasing the dosing interval. Children with newly-diagnosed disease may begin therapy, but no new adults will be enrolled in the Myozyme® Temporary Access Program (MTAP). Any physician who feels their patient is in urgent need of therapy may contact Genzyme Medical Information at (800) 745-4447, option 2.

Additional information may be found at:
http://www.myozyme.com/pdf/MTAP_Supply_Update_January%202009.pdf
http://www.myozyme.com/MTAP/mtap_pt.asp

U.S. BRAND NAMES — Myozyme®

PHARMACOLOGIC CATEGORY
Enzyme

DOSING: PEDIATRIC — Replacement therapy for Pompe disease (infantile onset): Children 1 month to 3.5 years (at first infusion): I.V.: 20 mg/kg over ~4 hours every 2 weeks

(For additional information see "Alglucosidase alfa: Pediatric drug information")

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution [preservative free]:
Myozyme®: 50 mg [contains mannitol 210 mg; polysorbate 80; derived from Chinese hamster ovary cells]

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [preservative free]:
Myozyme®: 50 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Infuse over ~4 hours; initiate at 1 mg/kg/hour. If tolerated, increase by 2 mg/kg/hour every 30 minutes to a maximum rate of 7 mg/kg/hour. Decrease rate or temporarily hold for infusion reactions. Infuse through a low protein-binding, 0.2 micron in-line filter.

COMPATIBILITY — Stable in NS; do not infuse with other products.

USE — Replacement therapy for Pompe disease (infantile onset)

ADVERSE REACTIONS SIGNIFICANT
>20%:
Cardiovascular: Tachycardia (23%), bradycardia (21%), flushing (21%)
Central nervous system: Fever (92%), pain (postprocedural: 26%)
Dermatologic: Rash (54%), diaper dermatitis (36%), urticaria (21%)
Gastrointestinal: Diarrhea (62%), vomiting (49%), gastroenteritis (41%), oral candidiasis (31%), gastroesophageal reflux (26%), constipation (23%)
Hematologic: Anemia (31%)
Local: Catheter-related infections (28%)
Otic: Otitis media (33% to 44%)
Respiratory: Cough (46%), pneumonia (46%), upper respiratory tract infection (44%), oxygen saturation decreased (41%), pharyngitis (36%), respiratory distress (33%), respiratory failure (31%), rhinorrhea (28%), bronchiolitis (23%), nasopharyngitis (23%), tachypnea (23%)
Miscellaneous: Antibodies to alglucosidase alfa (89%; may affect efficacy), infusion reaction (51%)

Frequency not reported and/or case reports: Abdominal pain, agitation, anaphylactic reactions, bronchospasm, cardiac arrest, cardiorespiratory failure, chest discomfort/pain, conjunctivitis, cyanosis, erythema, face edema, facial erythema, fatigue, fluid overload, headache, hyperhidrosis, hypersensitivity, hyper-/hypotension, irritability, lacrimation increased, livedo reticularis, malaise, muscle spasm, nausea, pallor, periorbital edema, peripheral edema, pruritus, respiratory syncytial virus infection, restlessness, retching, rhinitis, rigors, skin lesions (ulcerative/necrotizing), tremor, wheezing

CONTRAINDICATIONS — There are no contraindications listed in the manufacturer's labeling.

WARNINGS / PRECAUTIONS
Boxed warnings: Anaphylaxis/hypersensitivity reactions: See "Concerns related to adverse effects" below. Cardiovascular disease: See "Disease-related concerns" below. Respiratory disease: See "Disease-related concerns" below.

Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: [U.S. Boxed Warning]: Severe hypersensitivity reactions, including anaphylactic reactions and anaphylactic shock have been reported during and within 3 hours after infusion. Immediate medical support should be readily available. Immune-mediated reactions: Severe immune-mediated reactions (eg, ulcerative and necrotizing skin lesions, type-III immune complex-mediated reactions, inflammatory arthropathy) have occurred up to 3 years after initiation of therapy; monitor for development. Infusion reactions: Infusion-related reactions are common; discontinue immediately for severe hypersensitivity or anaphylactic reaction; mild-to-moderate reactions may be managed by reducing the infusion rate and/or administering antihistamines and/or antipyretics. Appropriate medical support for the management of infusion reactions should be readily available. Use caution with subsequent infusions; infusion reactions have occurred despite premedication with antihistamines, antipyretics, and/or steroids. Patients with acute underlying illness are at greater risk for infusion reactions, including cardiorespiratory failure.

Disease-related concerns: Cardiovascular disease: [U.S. Boxed Warning]: Use with caution in patients with compromised cardiac function; risk of acute cardiorespiratory failure secondary to infusion-related reactions may be increased. Additional monitoring is warranted. Cardiorespiratory failure has been observed in patients with cardiac hypertrophy up to 72 hours after infusion; arrhythmias have also been observed in patients with cardiac hypertrophy. Pompe disease: Safety and efficacy have not been established in juvenile-onset and adult-onset Pompe disease. Patients with Pompe disease are at increased risk for infusion-related cardiorespiratory failure (possibly due to fluid overload); monitor closely during infusion. Respiratory disease: [U.S. Boxed Warning]: Use with caution in patients with compromised respiratory function; risk of acute cardiorespiratory failure secondary to infusion-related reactions may be increased. Additional monitoring is warranted.

Other warnings/precautions: Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment; patients should be encouraged to register (www.pomperegistry.com or 1-800-745-4447).

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Animal studies have not demonstrated teratogenicity or fertility impairment. There are no adequate and well-controlled studies in pregnant women. A registry has been established for Pompe patients; women of childbearing potential are encouraged to enroll in the registry (www.pomperegistry.com or 1-800-745-4447).

LACTATION — Excretion in breast milk unknown/use caution

BREAST-FEEDING CONSIDERATIONS — A registry has been established for Pompe patients; women who are nursing are encouraged to enroll in the registry (www.pomperegistry.com or 1-800-745-4447)

MONITORING PARAMETERS — Liver enzymes (baseline and periodically; elevation may be due to disease process); vital signs during and following infusion; volume overload

The manufacturer recommends monitoring for IgG antibody formation every 3 months. No commercial tests are available; however, sampling kits can be obtained by contacting Genzyme Corporation at 1-800-745-4447.

INTERNATIONAL BRAND NAMES — Myozyme (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, IE, IL, IT, NL, NO, PT, RU, SE, TR, TW)

MECHANISM OF ACTION — Alglucosidase alfa is a recombinant form of the enzyme acid alpha-glucosidase (GAA), which is required for glycogen cleavage. Due to an inherited GAA deficiency, glycogen accumulates in the tissues of patients with Pompe disease, leading to progressive muscle weakness. In infantile-onset Pompe disease, glycogen accumulates in cardiac and skeletal muscles and hepatic tissue, leading to cardiomyopathy and respiratory failure. Juvenile- and adult-onset Pompe disease are limited to glycogen accumulation in skeletal muscle, leading to respiratory failure. Alglucosidase alfa binds to mannose-6-phosphate receptors on the cell surface, becomes internalized and transported to lysosomes resulting in increased enzymatic activity and glycogen cleavage.

PHARMACODYNAMICS / KINETICS
Distribution: Vss: 80-147 mL/kg

Half-life elimination: 2-3 hours

Basiliximab

U.S. BRAND NAMES — Simulect®

PHARMACOLOGIC CATEGORY
Monoclonal Antibody

DOSING: ADULTS — Note: Patients previously administered basiliximab should only be re-exposed to a subsequent course of therapy with extreme caution.

Renal transplantation: I.V.: 20 mg within 2 hours prior to transplant surgery, followed by a second 20 mg dose 4 days after transplantation. The second dose should be withheld if complications occur (including severe hypersensitivity reactions or graft loss).

DOSING: PEDIATRIC — Note: Patients previously administered basiliximab should only be re-exposed to a subsequent course of therapy with extreme caution.

(For additional information see "Basiliximab: Pediatric drug information")

Renal transplantation: I.V.:
Children <35 kg: 10 mg within 2 hours prior to transplant surgery, followed by a second 10 mg dose 4 days after transplantation; the second dose should be withheld if complications occur (including severe hypersensitivity reactions or graft loss)
Children ≥ 35 kg: Refer to adult dosing

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — No specific dosing adjustment is recommended.

DOSING: HEPATIC IMPAIRMENT — No specific dosing adjustment is recommended.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution [preservative free]:
Simulect®: 10 mg, 20 mg

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [preservative free]:
Simulect®: 10 mg, 20 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — For intravenous administration only. Infuse as a bolus or I.V. infusion over 20-30 minutes. (Bolus dosing is associated with nausea, vomiting, and local pain at the injection site.)

USE — Prophylaxis of acute organ rejection in renal transplantation

ADVERSE REACTIONS SIGNIFICANT — Administration of basiliximab did not appear to increase the incidence or severity of adverse effects in clinical trials. Adverse events were reported in 96% of both the placebo and basiliximab groups.

>10%:
Cardiovascular: Hypertension, peripheral edema
Central nervous system: Fever, headache, insomnia, pain
Dermatologic: Acne, wound complications
Endocrine & metabolic: Hypercholesterolemia, hyperglycemia, hyper-/hypokalemia, hyperuricemia, hypophosphatemia
Gastrointestinal: Abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting
Genitourinary: Urinary tract infection
Hematologic: Anemia
Neuromuscular & skeletal: Tremor
Respiratory: Dyspnea, infection (upper respiratory)
Miscellaneous: Viral infection

3% to 10%:
Cardiovascular: Abnormal heart sounds, angina pectoris, arrhythmia, atrial fibrillation, cardiac failure, chest pain, generalized edema, hypotension, tachycardia
Central nervous system: Agitation, anxiety, depression, dizziness, fatigue, hypoesthesia, malaise, neuropathy, rigors
Dermatologic: Cyst, hypertrichosis, pruritus, rash, skin disorder, skin ulceration
Endocrine & metabolic: Acidosis, dehydration, diabetes mellitus, fluid overload, hyper-/hypocalcemia, hyperlipidemia, hypertriglyceridemia, hypoglycemia, hypomagnesemia, hyponatremia
Gastrointestinal: Abdomen enlarged, esophagitis, flatulence, gastroenteritis, GI hemorrhage, gingival hyperplasia, melena, moniliasis, stomatitis (including ulcerative), weight gain
Genitourinary: Albuminuria, bladder disorder, dysuria, genital edema, hematuria, impotence, oliguria, renal function abnormal, renal tubular necrosis, ureteral disorder, urinary frequency, urinary retention
Hematologic: Hematoma, hemorrhage, leukopenia, polycythemia, purpura, thrombocytopenia, thrombosis
Neuromuscular & skeletal: Arthralgia, arthropathy, back pain, cramps, fracture, hernia, leg pain, myalgia, paresthesia, weakness
Ocular: Abnormal vision, cataract, conjunctivitis
Respiratory: Bronchitis, bronchospasm, cough, pharyngitis, pneumonia, pulmonary edema, sinusitis, rhinitis
Miscellaneous: Accidental trauma, facial edema, glucocorticoids increased, herpes infection, sepsis

Postmarketing and/or case reports: Capillary leak syndrome, cytokine release syndrome; severe hypersensitivity reactions, including anaphylaxis, have been reported (symptoms may include hypotension, tachycardia, cardiac failure, dyspnea, bronchospasm, pulmonary edema, urticaria, rash, pruritus, sneezing, and respiratory failure)

CONTRAINDICATIONS — Hypersensitivity to basiliximab, murine proteins, or any component of the formulation

WARNINGS / PRECAUTIONS
Boxed warnings: Experienced physician: See "Other warnings/precautions" below.

Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Severe hypersensitivity reactions, occurring within 24 hours, have been reported. Reactions, including anaphylaxis, have occurred both with the initial exposure and/or following re-exposure after several months; use caution during re-exposure to a subsequent course of therapy in a patient who has previously received basiliximab. Discontinue the drug permanently if a reaction occurs. Medications for the treatment of hypersensitivity reactions should be available for immediate use. Human antimurine antibodies (HAMA): Treatment may result in the development of HAMA; however, limited evidence suggesting the use of muromonab-CD3 or other murine products is not precluded. Lymphoproliferative disorders: The incidence of lymphoproliferative disorders may be increased by immunosuppressive therapy. Opportunistic infections: The incidence opportunistic infections may be increased by immunosuppressive therapy.

Other warnings/precautions: Appropriate use: To be used as a component of immunosuppressive regimen which includes cyclosporine and corticosteroids. Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of a physician experienced in immunosuppression therapy.

DRUG INTERACTIONS
Abciximab: May enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Risk C: Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy

Hypoglycemic Agents: May enhance the adverse/toxic effect of other Hypoglycemic Agents. Risk C: Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Echinacea may diminish the therapeutic effect of basiliximab. Avoid hypoglycemic herbs, including alfalfa, bilberry, bitter melon, burdock, celery, damiana, fenugreek, garcinia, garlic, ginger, ginseng, gymnema, marshmallow, and stinging nettle (may enhance the hypoglycemic effect of basiliximab).

PREGNANCY RISK FACTOR — B (show table) (manufacturer)

PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. IL-2 receptors play an important role in the development of the immune system. Use in pregnant women only when benefit exceeds potential risk to the fetus. Women of childbearing potential should use effective contraceptive measures before beginning treatment and for 4 months after completion of therapy with this agent.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — It is not known whether basiliximab is excreted in human milk. Because many immunoglobulins are secreted in milk and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

MONITORING PARAMETERS — Signs and symptoms of acute rejection

CANADIAN BRAND NAMES — Simulect®

INTERNATIONAL BRAND NAMES — Simulect (AR, AT, AU, BE, BG, BR, CH, CL, CN, CO, CZ, DE, DK, EC, ES, FI, FR, GB, GR, HK, HN, IE, IL, IT, KP, MX, MY, NL, NO, PE, PH, PK, PL, PT, PY, RU, SE, SG, TH, TR, TW, UY, VE)

MECHANISM OF ACTION — Chimeric (murine/human) monoclonal antibody which blocks the alpha-chain of the interleukin-2 (IL-2) receptor complex; this receptor is expressed on activated T lymphocytes and is a critical pathway for activating cell-mediated allograft rejection

PHARMACODYNAMICS / KINETICS
Duration: Mean: 36 days (determined by IL-2R alpha saturation)

Distribution: Mean: Vd: Children 1-11 years: 4.8 +/- 2.1 L; Adolescents 12-16 years: 7.8 +/- 5.1 L; Adults: 8.6 +/- 4.1 L

Half-life elimination: Children 1-11 years: 9.5 days; Adolescents 12-16 years: 9.1 days; Adults: Mean: 7.2 days

Excretion: Clearance: Children 1-11 years: 17 mL/hour; Adolescents 12-16 years: 31 mL/hour; Adults: Mean: 41 mL/hour

Barium

U.S. BRAND NAMES — Anatrast; Bar-Test; Baricon™ ; Baro-Cat®; Barobag®; Barosperse®; CheeTah®; E-Z-Cat®; E-Z-Cat® Dry; E-Z-Disk™ ; Enhancer; Entero Vu™ ; Entrobar®; EntroEase®; Esopho-Cat®; HD 200® Plus; Intropaste; Liqui-Coat HD®; Liquid Barosperse®; Medebar® Plus; Prepcat; Readi-Cat®; Readi-Cat® 2; Tomocat®; Tomocat® 1000; Tonojug; Tonopaque; Varibar® Honey; Varibar® Nectar; Varibar® Pudding; Varibar® Thin Honey; Varibar® Thin Liquid; VoLumen™

PHARMACOLOGIC CATEGORY
Radiopaque Agents

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Cream, oral, as sulfate:
Esopho-Cat®: 3% w/w (30 g) [contains sodium benzoate; vanilla flavor]

Paste, oral, as sulfate:
Varibar® Pudding: 40% w/v (230 mL) [target viscosity 5000 CPS; contains sodium benzoate; vanilla flavor]

Powder for suspension, oral, as sulfate:
Baricon™ : 98% w/w (340 g) [lemon-vanilla flavor]
Enhancer: 98% w/w (312 g) [lemon-vanilla flavor]
E-Z-Cat® Dry: 2% w/w (23 g) [provides 450 mL 2% w/w suspension after mixing; orange vanilla flavor]
HD 200® Plus: 98% w/w (312 g) [strawberry flavor]
Tonopaque: 95% w/w (180 g) [cherry flavor]
Varibar® Thin Liquid: 40% w/v (148 g) [provides 40% w/v suspension after mixing; target viscosity 4 CPS; apple flavor]

Powder for suspension, oral/rectal, as sulfate:
Barosperse®: 95% w/w (225 g, 900 g) [vanilla flavor]
Tonojug: 95% w/w (1200 g) [cherry flavor]

Powder for suspension, rectal, as sulfate:
Barobag®: 97% w/w (340 g, 454 g) [packaged as an enema kit]

Suspension, oral, as sulfate:
Entero Vu™ : 24% w/v (600 mL) [contains sodium benzoate; blueberry flavor]
EntroEase®: 13% w/v (600 mL) [contains sodium benzoate; marshmallow flavor]
E-Z-Cat®: 4.9% w/v (255 mL) [orange flavor]
Liqui-Coat HD®: 210% w/v (150 mL) [contains sodium benzoate; vanilla-raspberry flavor]
Readi-Cat® 2: 2.1% w/v ( 250 mL) [contains benzoic acid and sodium benzoate; banana smoothie flavor]; (450 mL) [contains benzoic acid and sodium benzoate; apple smoothie, banana smoothie, and berry smoothie flavors]
Varibar® Honey: 40% w/v (250 mL) [target viscosity 3000 CPS; contains sodium benzoate; apple flavor]
Varibar® Nectar: 40% w/v (240 mL) [target viscosity 300 CPS; contains sodium benzoate; apple flavor]
Varibar® Thin Honey: 40% w/v (250 mL) [target viscosity 1500 CPS; contains sodium benzoate; apple flavor]
VoLumen™ : 0.1% w/v (450 mL) [contains benzoic acid, sodium benzoate; blueberry flavor]

Suspension, oral/rectal, as sulfate:
Baro-Cat®: 1.5% w/v (300 mL, 900 mL) [banana-pineapple flavor]
CheeTah®: 2.2% w/w (450 mL, 900 mL) [contains sodium benzoate; butterscotch vanilla flavor]
Liquid Barosperse®: 60% w/v (355 mL) [vanilla flavor]
Prepcat: 1.5% w/v (450 mL) [strawberry flavor]
Readi-Cat®: 1.3% w/v (450 mL, 900 mL, 1900 mL) [contains sodium benzoate; orange vanilla flavor; also supplied as a Cat-Pak with enema tubing]
Readi-Cat® 2: 2.1% w/v (450 mL, 900 mL, 1900 mL) [contains sodium benzoate; orange vanilla flavor]
Tomocat®: 5% w/v (145 mL) [concentrate to make a 1.5% solution; strawberry flavor]
Tomocat® 1000: 5% w/v (225 mL) [concentrate; strawberry flavor]

Suspension paste, rectal:
Anatrast: 100% w/v (500 g) [suspension paste; packaged with enema tips]
Intropaste: 70% w/v (454 g) [raspberry flavor]

Suspension, rectal, as sulfate:
Entrobar®: 50% w/v (500 mL) [packaged in administration kit]
Medebar® Plus: 100% w/v (1900 mL)

Tablet, oral, as sulfate:
Bar-Test, E-Z-Disk™ : 648 mg

DOSAGE FORMS: CONCISE
Cream, oral:
Esopho-Cat®: 3% w/w

Paste, oral:

Varibar® Pudding: 40% w/v

Powder for suspension, oral:
Baricon™ , Enhancer, HD 200® Plus: 98% w/w
E-Z-Cat® Dry: 2% w/w
Tonopaque: 95% w/w
Varibar® Thin Liquid: 40% w/v

Powder for suspension, oral/rectal:
Barosperse®, Tonojug: 95% w/w

Powder for suspension, rectal:
Barobag®: 97% w/w

Suspension, oral:
Entero Vu™ : 24% w/v
EntroEase®: 13% w/v
E-Z-Cat®: 4.9% w/v
Liqui-Coat HD®: 210% w/v
Readi-Cat® 2: 2.1% w/v
Varibar® Honey, Varibar® Nectar, Varibar® Thin Honey: 40% w/v
VoLumen™ : 0.1% w/v

Suspension, oral/rectal:
Baro-Cat®, Prepcat: 1.5% w/v
CheeTah®: 2.2% w/w
Liquid Barosperse®: 60% w/v
Readi-Cat®: 1.3% w/v
Readi-Cat® 2: 2.1% w/v
Tomocat®, Tomocat® 1000: 5% w/v

Suspension, paste:
Anatrast: 100% w/v
Intropaste: 70% w/v

Suspension, rectal:
Entrobar®: 50% w/v
Medebar® Plus: 100% w/v

Tablet, oral, as sulfate:
Bar-Test, E-Z-Disk™ : 648 mg

GENERIC EQUIVALENT AVAILABLE — No

USE — Diagnostic aid for computed tomography or x-ray examinations of the GI tract

CONTRAINDICATIONS — Hypersensitivity to barium or any component of the formulation; known or suspected obstruction of the colon, known or suspected GI tract perforation, suspected tracheoesophageal fistula, obstructing lesions of small intestine, pyloric stenosis

Specific agents may also be contraindicated with inflammation or neoplastic lesions of the rectum, recent rectal biopsy; use in infants with swallowing disorders; newborns with complete duodenal or jejunal obstruction with suspected distal small bowel or colon obstruction; very small preterm infants and young babies requiring small volumes of contrast media; infants and young children with possible leakage from GI tract (eg, necrotizing enterocolitis, unexplained pneumoperitoneum, gasless abdomen, bowel or esophageal perforation, postoperative anastomosea)

PREGNANCY IMPLICATIONS — Safety and efficacy for use during pregnancy have not been established. In general, elective radiography of the abdomen is avoided during pregnancy unless essential for diagnosis.

BREAST-FEEDING CONSIDERATIONS — Barium sulfate is not systemically absorbed.

INTERNATIONAL BRAND NAMES — Barium Sulfuricum (PL); Falibaryt (PL); Micropaque (PL); Microtrast (PL); Prontobario (PL)

Balsalazide

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Colazal® may be confused with Clozaril®

U.S. BRAND NAMES — Colazal®

PHARMACOLOGIC CATEGORY
5-Aminosalicylic Acid Derivative
Anti-inflammatory Agent

DOSING: ADULTS — Ulcerative colitis: Oral: 2.25 g (three 750 mg capsules) 3 times/day for 8-12 weeks

DOSING: PEDIATRIC — Ulcerative colitis: Oral: Children 5-17 years: 750 mg 3 times/day for up to 8 weeks or 2.25 g (three 750 mg capsules) 3 times/day for 8 weeks

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — No information available with balsalazide; renal toxicity has been observed with other 5-aminosalicylic acid products; use with caution.

DOSING: HEPATIC IMPAIRMENT — No specific dosage adjustment available.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, as disodium: 750 mg
Colazal®: 750 mg [contains sodium ~86 mg/capsule]

DOSAGE FORMS: CONCISE
Capsule: 750 mg
Colazal®: 750 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Capsules should be swallowed whole or may be opened and sprinkled on applesauce. Applesauce mixture may be chewed; swallow immediately, do not store mixture for later use. When sprinkled on food, may cause staining of teeth or tongue.

USE — Treatment of mild-to-moderate active ulcerative colitis

ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Headache (children 15%; adults 8%)
Gastrointestinal: Abdominal pain (children 12% to 13%; adults 6%)

1% to 10%:
Central nervous system: Insomnia (adults 2%), fatigue (children 4%; adults 2%), fever (children 6%; adults 2%)
Endocrine & metabolic: Dysmenorrhea (children 3%)
Gastrointestinal: Diarrhea (children 9%; adults 5%), ulcerative colitis exacerbation (children 6%; adults 1%), nausea (children 4%; adults 5%), vomiting (children 10%; adults 4%), hematochezia (children 4%), stomatitis (children 3%), anorexia (adults 2%), dyspepsia (adults 2%), flatulence (adults 2%), cramps (adults 1%), constipation (adults 1%), xerostomia (adults 1%)
Genitourinary: Urinary tract infection (adults 1%)
Neuromuscular & skeletal: Arthralgia (adults 4%), back pain (adults 2%), myalgia (adults 1%)
Respiratory: Respiratory infection (adults 4%), cough (children 3%; adults 2%), pharyngitis (children 6%; adults 2%), pharyngolaryngeal pain (children 3%), rhinitis (adults 2%)
Miscellaneous: Flu-like syndrome (children 4%; adults 1%)

<1% (Limited to important or life-threatening): Alopecia, cholestatic jaundice, cirrhosis, hepatocellular damage, hepatotoxicity, jaundice, hypersensitivity pericarditis, Kawasaki-like syndrome, liver failure, liver necrosis, liver function tests increased, myocarditis

CONTRAINDICATIONS — Hypersensitivity to balsalazide, metabolites to balsalazide, salicylates, or any component of the formulation

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Colitis: May exacerbate symptoms of ulcerative colitis.

Disease-related concerns: Pyloric stenosis: Use with caution in patients with pyloric stenosis; prolonged gastric retention of capsules may occur, delaying release of drug in the colon. Renal impairment: Use with caution in patients with renal impairment; renal toxicity has been observed with other mesalamine (5-aminosalicylic acid) products.

Special populations: Pediatrics: Safety and efficacy have not been established in children <5 years of age.

Other warnings/precautions: Duration of therapy: Safety and efficacy of use beyond 12 weeks in adults or 8 weeks in children have not been established.

DRUG INTERACTIONS
Cardiac Glycosides: 5-ASA Derivatives may decrease the absorption of Cardiac Glycosides. Risk C: Monitor therapy

Thiopurine Analogs: 5-ASA Derivatives may decrease the metabolism of Thiopurine Analogs. Risk C: Monitor therapy

Varicella Virus-Containing Vaccines: 5-ASA Derivatives may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. The primary concern is the potential development of Reye's Syndrome, a condition that has been associated with the use of salicylates in children with varicella infections. Risk D: Consider therapy modification

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies have been done in pregnant women. Balsalazide should be used in pregnant women only if clearly needed.

LACTATION — Excretion in breast milk unknown/use caution

DIETARY CONSIDERATIONS — Colazal® 750 mg capsule contains sodium ~86 mg.

PRICING — (data from drugstore.com)
Capsules (Balsalazide Disodium)
750 mg (280): $319.98

Capsules (Colazal)
750 mg (280): $449.96

MONITORING PARAMETERS — Improvement or worsening of symptoms

INTERNATIONAL BRAND NAMES — Balzide (IT); Basazyde (TW); Benoquin (AR); Calazide (AU); Colazal (KP); Colazid (NO, SE); Colazide (AT, GB); Garian (UY); Premid (DK)

MECHANISM OF ACTION — Balsalazide is a prodrug, converted by bacterial azoreduction to 5-aminosalicylic acid (mesalamine, active), 4-aminobenzoyl-ß-alanine (inert), and their metabolites. 5-aminosalicylic acid may decrease inflammation by blocking the production of arachidonic acid metabolites topically in the colon mucosa.

PHARMACODYNAMICS / KINETICS
Onset of action: Delayed; may require several days to weeks

Absorption: Very low and variable

Protein binding: Balsalazide: ≥ 99%

Metabolism: Azoreduced in the colon to 5-aminosalicylic acid (active), 4-aminobenzoyl-ß-alanine (inert), and N-acetylated metabolites

Half-life elimination: Primary effect is topical (colonic mucosa); systemic half-life not determined

Time to peak: Balsalazide: 1-2 hours

Excretion: Feces (65% as 5-aminosalicylic acid, 4-aminobenzoyl-ß-alanine, and N-acetylated metabolites); urine (25% as N-acetylated metabolites); Parent drug: Urine or feces (<1%)

PATIENT INFORMATION — Capsules should be swallowed whole or may be opened and sprinkled on applesauce. Report abdominal pain, unresolved diarrhea, severe headache, or chest pain to prescriber.

Balanced salt solution

PHARMACOLOGIC CATEGORY
Irrigating Solution
Ophthalmic Agent, Miscellaneous

DOSING: ADULTS — Irrigation: Based on standard for each surgical procedure

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, irrigation [preservative free]: Sodium chloride 0.64%, potassium chloride 0.075%, calcium chloride 0.048%, magnesium chloride 0.03%, sodium acetate 0.39%, sodium citrate 0.17% (500 mL)

Solution, ophthalmic [irrigation; preservative free]: Sodium chloride 0.64%, potassium chloride 0.075%, calcium chloride 0.048%, magnesium chloride 0.03%, sodium acetate 0.39%, sodium citrate 0.17% (18 mL, 500 mL)
AquaLase™ : Sodium chloride 0.64%, potassium chloride 0.075%, calcium chloride 0.048%, magnesium chloride 0.03%, sodium acetate 0.39%, sodium citrate 0.17% (90 mL)
BSS®: Sodium chloride 0.64%, potassium chloride 0.075%, calcium chloride 0.048%, magnesium chloride 0.03%, sodium acetate 0.39%, sodium citrate 0.17% (15 mL, 30 mL, 250 mL, 500 mL)
BSS Plus®: Sodium chloride 0.71%, potassium chloride 0.038%, calcium chloride 0.015%, magnesium chloride 0.02%, sodium phosphate 0.042%, sodium bicarbonate 0.21%, dextrose 0.092%, glutathione 0.018% (250 mL, 500 mL)
Navstel®: Sodium chloride 0.71%, potassium chloride 0.038%, calcium chloride 0.015%, magnesium chloride 0.02%, sodium phosphate 0.042%, sodium bicarbonate 0.21%, dextrose 0.092%, glutathione 0.018%, hypromellose 0.125% to 0.173% (250 mL, 500 mL)

DOSAGE FORMS: CONCISE
Solution, irrigation [preservative free]: Sodium chloride 0.64%, potassium chloride 0.075%, calcium chloride 0.048%, magnesium chloride 0.03%, sodium acetate 0.39%, sodium citrate 0.17% (500 mL)

Solution, ophthalmic [irrigation; preservative free]: Sodium chloride 0.64%, potassium chloride 0.075%, calcium chloride 0.048%, magnesium chloride 0.03%, sodium acetate 0.39%, sodium citrate 0.17% (18 mL, 500 mL)
AquaLase™ : Sodium chloride 0.64%, potassium chloride 0.075%, calcium chloride 0.048%, magnesium chloride 0.03%, sodium acetate 0.39%, sodium citrate 0.17% (90 mL)
BSS®: Sodium chloride 0.64%, potassium chloride 0.075%, calcium chloride 0.048%, magnesium chloride 0.03%, sodium acetate 0.39%, sodium citrate 0.17% (15 mL, 30 mL, 250 mL, 500 mL)
BSS Plus®: Sodium chloride 0.71%, potassium chloride 0.038%, calcium chloride 0.015%, magnesium chloride 0.02%, sodium phosphate 0.042%, sodium bicarbonate 0.21%, dextrose 0.092%, glutathione 0.018% (250 mL, 500 mL)
Navstel®: Sodium chloride 0.71%, potassium chloride 0.038%, calcium chloride 0.015%, magnesium chloride 0.02%, sodium phosphate 0.042%, sodium bicarbonate 0.21%, dextrose 0.092%, glutathione 0.018%, hypromellose 0.125% to 0.173% (250 mL, 500 mL)

GENERIC EQUIVALENT AVAILABLE — Yes

USE
Irrigation solution for ophthalmic surgery:
AquaLase™ , BSS®: Intraocular or extraocular irrigating solution
BSS Plus®, Navstel®: Intraocular irrigating solution

Irrigation solution for eyes, ears, nose, or throat

ADVERSE REACTIONS SIGNIFICANT
>10%: Ocular: Intraocular pressure increased (11% to 12%), cataract (7% to 11%)

1% to 10%:
Central nervous system: Headache (3%)
Ocular: Discomfort (3% to 5%), dry eyes (3% to 5%), macular edema (4%), conjunctival hyperemia (3% to 4%), posterior capsule opacification (2% to 3%), iritis (1% to 3%), retinal hemorrhage (1% to 3%), blurred vision (1% to 2%)

CONTRAINDICATIONS — Injection or I.V. infusion; use during electrosurgical procedures

WARNINGS / PRECAUTIONS
Disease-related concerns: Diabetes: Use with caution in patients with diabetes mellitus; intraoperative lens changes have been observed when undergoing vitrectomy procedure.

Other warnings/precautions: Appropriate use: For use during surgical procedures with an expected duration ≤ 60 minutes.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — C (show table)

LACTATION — Excretion in breast milk unknown/use caution

CANADIAN BRAND NAMES — BSS Plus®; BSS®; Eye-Stream®

INTERNATIONAL BRAND NAMES — Balanced Salt Solution (DK, FI, GB, NZ)