U.S. BRAND NAMES — Amikin®
PHARMACOLOGIC CATEGORY Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW) In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW) Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery)
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Hospital-acquired pneumonia (HAP): 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW) In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW) Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Individualization is critical because of the low therapeutic index. Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients). Clcr 60 mL/minute: Administer every 8 hours Clcr 40-60 mL/minute: Administer every 12 hours Clcr 20-40 mL/minute: Administer every 24 hours Clcr <20 mL/minute: Loading dose, then monitor levels
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution, as sulfate: 50 mg/mL (2 mL, 4 mL); 62.5 mg/mL (8 mL) [DSC]; 250 mg/mL (2 mL, 4 mL) Amikin®: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL) [contains metabisulfite]
DOSAGE FORMS: CONCISE Injection, solution: 50 mg/mL (2 mL, 4 mL); 250 mg/mL (2 mL, 4 mL) Amikin®: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in dextran 75 6% in NS, D5LR, D51/4NS, D51/3NS, D51/2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, 1/4NS, 1/2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions.
Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol.
Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin.
Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Neurotoxicity Otic: Ototoxicity (auditory), ototoxicity (vestibular) Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS Box Warnings: Nephrotoxicity: See "Concerns related to adverse effects" below. Neuromuscular blockade and respiratory paralysis: See "Concerns related to adverse effects" below. Neurotoxicity: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in superinfection, including pseudomembranous colitis.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
DRUG INTERACTIONS Decreased effect of aminoglycoside: High concentrations of penicillins and/or cephalosporins (in vitro data)
Increased toxicity of aminoglycoside: Indomethacin I.V., amphotericin, loop diuretics, vancomycin, enflurane, methoxyflurane; increased effect of neuromuscular-blocking agents and polypeptide antibiotics with administration of aminoglycosides
PREGNANCY RISK FACTOR — D (show table)
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
Although breast-feeding is not recommended by the manufacturer, based on available data, amikacin is generally considered compatible (low risk to infant) while breast-feeding [human data].
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosidesin vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
REFERENCE RANGE Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels: Peak: Life-threatening infections: 25-40 mcg/mL Serious infections: 20-25 mcg/mL Urinary tract infections: 15-20 mcg/mL Trough: Serious infections: <8 mcg/mL Life-threatening infections: <8 mcg/mL The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include ototoxicity, nephrotoxicity, and neuromuscular toxicity. Treatment of choice, following a single acute overdose, appears to be the maintenance of good urine output of at least 3 mL/kg/hour. Dialysis is of questionable value in the enhancement of aminoglycoside elimination. If required, hemodialysis is preferred over peritoneal dialysis in patients with normal renal function.
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Akacin (TH); Akicin (TH); Akim (EC); Alostil (ID); Amicacina (ES); Amicasil (IT); Amicin (IN); Amikacin Sulfate Injection, USP (CA); Amikacina (CL); Amikafur (MX); Amikan (IT); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CA, CH, CI, CO, CZ, EC, EE, ET, GB, GH, GM, GN, HK, HU, ID, IE, KE, KR, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TW, TZ, UG, ZA, ZM, ZW); Amiklin (FR); Amikozit (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amiktam (KR); Amukin (BE, NL); Biklin (AR, AT, DE, DK, FI, PH, SE, VE); Biodacyna (PL); Biokacin (PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kanbine (ES); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lukadin (IT); Miacin (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Nica (PH); Novamin (BR); Orlobin (GR); Pierami (TW); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, MY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS Absorption: I.M.: Rapid Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs) CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent): Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours Children: 1.6-2.5 hours Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head.
Sunday, May 11, 2008
Amifostine
U.S. BRAND NAMES — Ethyol®
PHARMACOLOGIC CATEGORY Adjuvant, Chemoprotective Agent (Cytoprotective)Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 740-910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy Note: Doses >740 mg/m2 are associated with a higher incidence of hypotension and may require interruption of therapy or dose modification for subsequent cycles. For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule: The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below: Decrease of 20 mm Hg if baseline systolic blood pressure <100 Decrease of 25 mm Hg if baseline systolic blood pressure 100-119 Decrease of 30 mm Hg if baseline systolic blood pressure 120-139 Decrease of 40 mm Hg if baseline systolic blood pressure 140-179 Decrease of 50 mm Hg if baseline systolic blood pressure 180 If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.
Xerostomia from head and neck cancer, reduction: I.V.: 200 mg/m2/day over 3 minutes 15-30 minutes prior to radiation therapy or SubQ (unlabeled route): 500 mg/day prior to radiation therapy
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: Ethyol®: 500 mg
DOSAGE FORMS: CONCISE Injection, powder for reconstitution: Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — I.V.: Administer over 3-15 minutes; administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, netilmicin, ondansetron, piperacillin, plicamycin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin, ticarcillin/clavulanate, tobramycin, trimetrexate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, cefoperazone, chlorpromazine, cisplatin, ganciclovir, hydroxyzine, minocycline, prochlorperazine edisylate.
USE — Reduce the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Hypotension (15% to 62%; grades 3/4: 3% to 8%; dose dependent) Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypocalcemia, hypoxia, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria
CONTRAINDICATIONS — Hypersensitivity to amifostine, aminothiol compounds, or any component of the formulation
WARNINGS / PRECAUTIONS — Patients who are hypotensive or dehydrated should not receive amifostine. Interrupt antihypertensive therapy for 24 hours before amifostine. Patients who cannot safely stop their antihypertensives 24 hours before amifostine should not receive it. Patients should be adequately hydrated prior to amifostine infusion and kept in a supine position during the infusion. Blood pressure should be monitored every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line; subsequent infusions may require a dose reduction. Use caution in patients with cardiovascular and cerebrovascular disease and any other patients in whom the adverse effects of hypotension and nausea/vomiting may have serious adverse events.
It is recommended that antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist be administered prior to and in conjunction with amifostine. Rare hypersensitivity reactions, including anaphylaxis and severe cutaneous reaction, have been reported with a higher frequency in patients receiving amifostine as a radioprotectant. Discontinue if allergic reaction occurs; do not rechallenge.
Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome. Safety and efficacy in children have not been established.
DRUG INTERACTIONS — Antihypertensives: May potentiate the hypotensive effects of amifostine.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
MONITORING PARAMETERS — Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include hypotension, nausea, vomiting, anxiety and reversible urinary retention. Treatment includes infusion of normal saline for hypotension and supportive measures as clinically indicated.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Cytofos (TH); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CA, CL, CR, CZ, DE, DK, DO, EC, ES, FR, GB, GT, HK, HN, IE, IL, IT, MX, NI, NL, NZ, PA, PE, PH, PL, SG, SV, TH, UY, VE); Ethyol 500 (ZA)
MECHANISM OF ACTION — Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated in tissues.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: 8-9 minutes
Excretion: Urine Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.
PHARMACOLOGIC CATEGORY Adjuvant, Chemoprotective Agent (Cytoprotective)Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 740-910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy Note: Doses >740 mg/m2 are associated with a higher incidence of hypotension and may require interruption of therapy or dose modification for subsequent cycles. For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule: The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below: Decrease of 20 mm Hg if baseline systolic blood pressure <100 Decrease of 25 mm Hg if baseline systolic blood pressure 100-119 Decrease of 30 mm Hg if baseline systolic blood pressure 120-139 Decrease of 40 mm Hg if baseline systolic blood pressure 140-179 Decrease of 50 mm Hg if baseline systolic blood pressure 180 If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.
Xerostomia from head and neck cancer, reduction: I.V.: 200 mg/m2/day over 3 minutes 15-30 minutes prior to radiation therapy or SubQ (unlabeled route): 500 mg/day prior to radiation therapy
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: Ethyol®: 500 mg
DOSAGE FORMS: CONCISE Injection, powder for reconstitution: Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — I.V.: Administer over 3-15 minutes; administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, netilmicin, ondansetron, piperacillin, plicamycin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin, ticarcillin/clavulanate, tobramycin, trimetrexate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, cefoperazone, chlorpromazine, cisplatin, ganciclovir, hydroxyzine, minocycline, prochlorperazine edisylate.
USE — Reduce the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Hypotension (15% to 62%; grades 3/4: 3% to 8%; dose dependent) Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypocalcemia, hypoxia, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria
CONTRAINDICATIONS — Hypersensitivity to amifostine, aminothiol compounds, or any component of the formulation
WARNINGS / PRECAUTIONS — Patients who are hypotensive or dehydrated should not receive amifostine. Interrupt antihypertensive therapy for 24 hours before amifostine. Patients who cannot safely stop their antihypertensives 24 hours before amifostine should not receive it. Patients should be adequately hydrated prior to amifostine infusion and kept in a supine position during the infusion. Blood pressure should be monitored every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line; subsequent infusions may require a dose reduction. Use caution in patients with cardiovascular and cerebrovascular disease and any other patients in whom the adverse effects of hypotension and nausea/vomiting may have serious adverse events.
It is recommended that antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist be administered prior to and in conjunction with amifostine. Rare hypersensitivity reactions, including anaphylaxis and severe cutaneous reaction, have been reported with a higher frequency in patients receiving amifostine as a radioprotectant. Discontinue if allergic reaction occurs; do not rechallenge.
Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome. Safety and efficacy in children have not been established.
DRUG INTERACTIONS — Antihypertensives: May potentiate the hypotensive effects of amifostine.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
MONITORING PARAMETERS — Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include hypotension, nausea, vomiting, anxiety and reversible urinary retention. Treatment includes infusion of normal saline for hypotension and supportive measures as clinically indicated.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Cytofos (TH); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CA, CL, CR, CZ, DE, DK, DO, EC, ES, FR, GB, GT, HK, HN, IE, IL, IT, MX, NI, NL, NZ, PA, PE, PH, PL, SG, SV, TH, UY, VE); Ethyol 500 (ZA)
MECHANISM OF ACTION — Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated in tissues.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: 8-9 minutes
Excretion: Urine Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.
Amcinonide
U.S. BRAND NAMES — Cyclocort® [DSC]
PHARMACOLOGIC CATEGORY Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply in a thin film 2-3 times/day. Therapy should be discontinued when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol]
Lotion: 0.1% (60 mL) Cyclocort®: 0.1% (20 mL, 60 mL) [contains benzyl alcohol] [DSC]
Ointment: 0.1% (30 g, 60 g) [contains benzyl alcohol] Cyclocort®: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol] [DSC]
DOSAGE FORMS: CONCISE Cream: 0.1% (15 g, 30 g, 60 g)
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (high potency corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, hypopigmentation, allergic dermatitis, maceration of the skin, skin atrophy, striae, miliaria, telangiectasia
Endocrine & metabolic: Cushing's syndrome, growth retardation (long-term use), HPA suppression, hyperglycemia; these reactions occur more frequently with occlusive dressings
Local: Burning, itching, irritation, dryness, folliculitis, hypertrichosis
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to amcinonide or any component of the formulation; use on the face, groin, or axilla
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Disease-related concerns: Infected/weeping lesions: Occlusive dressings should not be used in presence of infection or weeping lesions.
Special populations: Pediatrics: Chronic use of corticosteroids in children may interfere with growth and development.
DRUG INTERACTIONS — No data reported
PREGNANCY RISK FACTOR — C (show table)
PRICING — (data from drugstore.com)Cream (Amcinonide) 0.1% (15): $20.99 0.1% (30): $26.99 0.1% (60): $45.99
Cream (Cyclocort) 0.1% (30): $32.99 0.1% (60): $53.99
Lotion (Cyclocort) 0.1% (20): $27.99 0.1% (60): $47.99
Ointment (Amcinonide) 0.1% (60): $43.99
Ointment (Cyclocort) 0.1% (15): $24.99 0.1% (30): $32.99 0.1% (60): $53.99
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms with long-term use only include cushingoid appearance (systemic), muscle weakness (systemic), and osteoporosis (systemic). When consumed in excessive quantities for prolonged periods, systemic hypercorticism and adrenal suppression may occur. In those cases, discontinuation and withdrawal of the corticosteroid should be done judiciously.
CANADIAN BRAND NAMES — Amcort®; Cyclocort®; ratio-Amcinonide; Taro-Amcinonide
INTERNATIONAL BRAND NAMES — Amciderm (DE, TH); Amcort (CA); Cyclocort (CA); ratio-Amcinonide (CA); Taro-Amcinonide (CA); Visderm (JP)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS Absorption: Adequate through intact skin; increases with skin inflammation or occlusion
Metabolism: Hepatic
Excretion: Urine and feces
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
PHARMACOLOGIC CATEGORY Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply in a thin film 2-3 times/day. Therapy should be discontinued when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol]
Lotion: 0.1% (60 mL) Cyclocort®: 0.1% (20 mL, 60 mL) [contains benzyl alcohol] [DSC]
Ointment: 0.1% (30 g, 60 g) [contains benzyl alcohol] Cyclocort®: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol] [DSC]
DOSAGE FORMS: CONCISE Cream: 0.1% (15 g, 30 g, 60 g)
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (high potency corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, hypopigmentation, allergic dermatitis, maceration of the skin, skin atrophy, striae, miliaria, telangiectasia
Endocrine & metabolic: Cushing's syndrome, growth retardation (long-term use), HPA suppression, hyperglycemia; these reactions occur more frequently with occlusive dressings
Local: Burning, itching, irritation, dryness, folliculitis, hypertrichosis
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to amcinonide or any component of the formulation; use on the face, groin, or axilla
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Disease-related concerns: Infected/weeping lesions: Occlusive dressings should not be used in presence of infection or weeping lesions.
Special populations: Pediatrics: Chronic use of corticosteroids in children may interfere with growth and development.
DRUG INTERACTIONS — No data reported
PREGNANCY RISK FACTOR — C (show table)
PRICING — (data from drugstore.com)Cream (Amcinonide) 0.1% (15): $20.99 0.1% (30): $26.99 0.1% (60): $45.99
Cream (Cyclocort) 0.1% (30): $32.99 0.1% (60): $53.99
Lotion (Cyclocort) 0.1% (20): $27.99 0.1% (60): $47.99
Ointment (Amcinonide) 0.1% (60): $43.99
Ointment (Cyclocort) 0.1% (15): $24.99 0.1% (30): $32.99 0.1% (60): $53.99
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms with long-term use only include cushingoid appearance (systemic), muscle weakness (systemic), and osteoporosis (systemic). When consumed in excessive quantities for prolonged periods, systemic hypercorticism and adrenal suppression may occur. In those cases, discontinuation and withdrawal of the corticosteroid should be done judiciously.
CANADIAN BRAND NAMES — Amcort®; Cyclocort®; ratio-Amcinonide; Taro-Amcinonide
INTERNATIONAL BRAND NAMES — Amciderm (DE, TH); Amcort (CA); Cyclocort (CA); ratio-Amcinonide (CA); Taro-Amcinonide (CA); Visderm (JP)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS Absorption: Adequate through intact skin; increases with skin inflammation or occlusion
Metabolism: Hepatic
Excretion: Urine and feces
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
Ambenonium
U.S. BRAND NAMES — Mytelase®
PHARMACOLOGIC CATEGORY Cholinergic Agonist
DOSING: ADULTS — Myasthenia gravis: Oral: 5-25 mg 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, as chloride [scored]: Mytelase®: 10 mg
DOSAGE FORMS: CONCISE Caplet [scored]: Mytelase®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of myasthenia gravis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmias (especially bradycardia), hypotension, carbon monoxide decreased, tachycardia, AV block, nodal rhythm, ECG changes (nonspecific), cardiac arrest, syncope, flushing
Central nervous system: Convulsions, dysarthria, dysphonia, dizziness, loss of consciousness, drowsiness, headache
Dermatologic: Skin rash, thrombophlebitis (I.V.), urticaria
Gastrointestinal: Hyperperistalsis, nausea, vomiting, salivation, diarrhea, stomach cramps, dysphagia, flatulence
Genitourinary: Urinary urgency
Neuromuscular & skeletal: Weakness, fasciculations, muscle cramps, spasms, arthralgia
Ocular: Small pupils, lacrimation
Respiratory: Bronchial secretions increased, laryngospasm, bronchiolar constriction, respiratory muscle paralysis, dyspnea, respiratory depression, respiratory arrest, bronchospasm
Miscellaneous: Diaphoresis increased, anaphylaxis, allergic reactions
CONTRAINDICATIONS — Routine administration of atropine or other belladonna alkaloids with ambenonium is contraindicated because they may suppress the muscarinic symptoms of excessive gastrointestinal stimulation, leaving only the more serious symptoms of muscle fasciculations and paralysis as signs of overdosage; should not be administered to patients receiving mecamylamine
WARNINGS / PRECAUTIONS — Prolonged action after cholinergics; drug should be discontinued until the patient is stabilized. Use with caution in patients with asthma, epilepsy, bradycardia, hyperthyroidism, or peptic ulcer. Differentiation of cholinergic/myasthenia crisis is critical; use edrophonium and clinical judgment. Anticholinergic insensitivity may develop for brief or prolonged periods. Reduce or withhold dosages until the patient becomes sensitive again. May require respiratory support.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/not recommended
PRICING — (data from drugstore.com)Tablets (Mytelase) 10 mg (100): $134.76
CANADIAN BRAND NAMES — Mytelase®
INTERNATIONAL BRAND NAMES — Mytelase (CA, PL); Mytelase Chloride (CZ, FR, HU, SE)
PHARMACOLOGIC CATEGORY Cholinergic Agonist
DOSING: ADULTS — Myasthenia gravis: Oral: 5-25 mg 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, as chloride [scored]: Mytelase®: 10 mg
DOSAGE FORMS: CONCISE Caplet [scored]: Mytelase®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of myasthenia gravis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmias (especially bradycardia), hypotension, carbon monoxide decreased, tachycardia, AV block, nodal rhythm, ECG changes (nonspecific), cardiac arrest, syncope, flushing
Central nervous system: Convulsions, dysarthria, dysphonia, dizziness, loss of consciousness, drowsiness, headache
Dermatologic: Skin rash, thrombophlebitis (I.V.), urticaria
Gastrointestinal: Hyperperistalsis, nausea, vomiting, salivation, diarrhea, stomach cramps, dysphagia, flatulence
Genitourinary: Urinary urgency
Neuromuscular & skeletal: Weakness, fasciculations, muscle cramps, spasms, arthralgia
Ocular: Small pupils, lacrimation
Respiratory: Bronchial secretions increased, laryngospasm, bronchiolar constriction, respiratory muscle paralysis, dyspnea, respiratory depression, respiratory arrest, bronchospasm
Miscellaneous: Diaphoresis increased, anaphylaxis, allergic reactions
CONTRAINDICATIONS — Routine administration of atropine or other belladonna alkaloids with ambenonium is contraindicated because they may suppress the muscarinic symptoms of excessive gastrointestinal stimulation, leaving only the more serious symptoms of muscle fasciculations and paralysis as signs of overdosage; should not be administered to patients receiving mecamylamine
WARNINGS / PRECAUTIONS — Prolonged action after cholinergics; drug should be discontinued until the patient is stabilized. Use with caution in patients with asthma, epilepsy, bradycardia, hyperthyroidism, or peptic ulcer. Differentiation of cholinergic/myasthenia crisis is critical; use edrophonium and clinical judgment. Anticholinergic insensitivity may develop for brief or prolonged periods. Reduce or withhold dosages until the patient becomes sensitive again. May require respiratory support.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/not recommended
PRICING — (data from drugstore.com)Tablets (Mytelase) 10 mg (100): $134.76
CANADIAN BRAND NAMES — Mytelase®
INTERNATIONAL BRAND NAMES — Mytelase (CA, PL); Mytelase Chloride (CZ, FR, HU, SE)
Amantadine
SPECIAL ALERTS Updated Influenza Guidelines - January 16, 2006
The Center for Disease Control (CDC) has made an interim recommendation to the 2005-2006 Influenza Guidelines. Due to increased resistance reported during the beginning of this season, the CDC is recommending that amantadine and rimantadine no longer be used for the treatment or prophylaxis of influenza A in the United States. If an antiviral medication is needed, oseltamivir or zanamivir should be used. Amantadine may still be used for its other approved indications, such as in the treatment of Parkinson's disease.
For additional information, refer to the following CDC website: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm55d117a1.htm?s_cid=mm55d117a1_e
U.S. BRAND NAMES — Symmetrel®
PHARMACOLOGIC CATEGORY Anti-Parkinson's Agent, Dopamine AgonistAntiviral Agent, Adamantane
DOSING: ADULTS Influenza A treatment: Oral: 100 mg twice daily; initiate within 24-48 hours after onset of symptoms; discontinue as soon as possible based on clinical response (generally within 3-5 days or within 24-48 hours after symptoms disappear).
Influenza A prophylaxis: Oral: 100 mg twice daily; continue treatment throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.
Drug-induced extrapyramidal symptoms: Oral: 100 mg twice daily; may increase to 300-400 mg/day, if needed
Parkinson's disease or Creutzfeldt-Jakob disease (unlabeled use): Oral: 100 mg twice daily as sole therapy; may increase to 400 mg/day if needed with close monitoring; initial dose: 100 mg/day if with other serious illness or with high doses of other anti-Parkinson drugs
DOSING: PEDIATRIC
(For additional information see "Amantadine: Pediatric drug information")Influenza A treatment: Oral: Note: Initiate within 24-48 hours after onset of symptoms; discontinue as soon as possible based on clinical response (generally within 3-5 days or within 24-48 hours after symptoms disappear) 1-9 years: 5 mg/kg/day in 2 divided doses (manufacturers range: 4.4-8.8 mg/kg/day); maximum dose: 150 mg/day 10 years and <40 kg: 5 mg/kg/day; maximum dose: 150 mg/day 10 years and 40 kg: Refer to adult dosing.
Influenza A prophylaxis: Oral: Refer to "Influenza A treatment" dosing. Continue treatment throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed. For children <9 years receiving influenza vaccine for the first time, amantadine prophylaxis should continue for 6 weeks (4 weeks after the first dose and 2 weeks after the second dose)
DOSING: ELDERLY — Adjust dose based on renal function; some patients tolerate the drug better when it is given in 2 divided daily doses (to avoid adverse neurologic reactions).
Influenza A prophylaxis or treatment: 100 mg/day in patients 65 years
DOSING: RENAL IMPAIRMENT Clcr 30-50 mL/minute: Administer 200 mg on day 1, then 100 mg/day
Clcr 15-29 mL/minute: Administer 200 mg on day 1, then 100 mg on alternate days
Clcr <15 mL/minute: Administer 200 mg every 7 days
Hemodialysis: Administer 200 mg every 7 days
Peritoneal dialysis: No supplemental dose is needed
Continuous arteriovenous or venous-venous hemofiltration: No supplemental dose is needed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 100 mg
Syrup, as hydrochloride: 50 mg/5 mL (480 mL)
Tablet, as hydrochloride: 100 mg Symmetrel®: 100 mg
DOSAGE FORMS: CONCISE Capsule: 100 mg
Syrup: 50 mg/5 mL
Tablet: 100 mg Symmetrel®: 100 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Prophylaxis and treatment of influenza A viral infection (per manufacturer labeling; also refer to current CDC guidelines for recommendations during current flu season); treatment of parkinsonism; treatment of drug-induced extrapyramidal symptoms
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Cardiovascular: Orthostatic hypotension, peripheral edema Central nervous system: Agitation, anxiety, ataxia, confusion, delirium, depression, dizziness, dream abnormality, fatigue, hallucinations, headache, insomnia, irritability, nervousness, somnolence Dermatologic: Livedo reticularis Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia Respiratory: Dry nose
<1% (Limited to important or life-threatening): Aggressive behavior, agranulocytosis, allergic reaction, amnesia, anaphylaxis, arrhythmia, cardiac arrest, CHF, coma, delirium, delusions, diaphoresis, dysphagia, dyspnea, eczematoid dermatitis, euphoria, hyperkinesis, leukopenia, mania, neutropenia, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), oculogyric episodes, paresthesia, photosensitivity, psychosis, pulmonary edema, rash, respiratory failure (acute), seizures, suicidal ideation, suicide, urinary retention, withdrawal reactions (may include delirium, hallucinations, and psychosis), visual disturbances
CONTRAINDICATIONS — Hypersensitivity to amantadine, rimantadine, or any component of the formulation
WARNINGS / PRECAUTIONS — Use with caution in patients with liver disease, history of recurrent and eczematoid dermatitis, uncontrolled psychosis or severe psychoneurosis, seizures, and in those receiving CNS-stimulant drugs; reduce dose in renal disease. When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months. Elderly patients may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation). Has not been shown to prevent bacterial infection or complications when used as prophylaxis or treatment of influenza A. Use with caution in patients with CHF, peripheral edema, or orthostatic hypotension. Avoid in untreated angle closure glaucoma. Due to increased resistance, in June 2006, the CDC recommended that amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established.
DRUG INTERACTIONS Anticholinergics may potentiate CNS side effects of amantadine; monitor for altered response; includes benztropine and trihexyphenidyl, as well as agents with anticholinergic activity (eg, quinidine, tricyclics, and antihistamines).
Antipsychotics (typical): May reduce the anti-Parkinsonian effects of amantadine
Triamterene: Has been reported to increase the potential for toxicity with amantadine (limited documentation); monitor response.
Vaccine: Influenza (live, attenuated): The live, attenuated form of influenza vaccine (administered intranasally) should not be administered within 2 weeks before or 48 hours after amantadine (unless medically indicated). Inactivated vaccine (trivalent) may be administered without concern to patients receiving amantadine.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase CNS adverse effects).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were observed in animal studies; limited data in humans. Impaired fertility has also been reported during animal studies and during human in vitro fertilization.
LACTATION — Enters breast milk/not recommended
PRICING — (data from drugstore.com)Syrup (Amantadine HCl) 50 mg/5 mL (120): $15.99
Syrup (Symmetrel) 50 mg/5 mL (120): $36.23
Tablets (Symmetrel) 100 mg (60): $82.09
MONITORING PARAMETERS — Renal function, Parkinson's symptoms, mental status, influenza symptoms, blood pressure
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose are generally consistent with excessive anticholinergic effects and include nausea, vomiting, slurred speech, blurred vision, lethargy, hallucinations, seizures, myoclonic jerking, and ventricular arrhythmias. Acute toxicity may be primarily due to anticholinergic effects. The minimum lethal dose may be as low as 1 g. Treatment should be supportive and directed at reducing CNS stimulation, controlling seizures, and maintaining cardiovascular function.
CANADIAN BRAND NAMES — Endantadine®; PMS-Amantadine; Symmetrel®
INTERNATIONAL BRAND NAMES — a.m.t. (DE); Amanda (TW); Amandin (TW); Amandine (UY); Amantadin (EE); Amantadin-ratiopharm (PL); Amantan (BE); Amantix (CO, PL); Amantrel (IN); Amazolon (JP); Atarin (FI); Boidan (JP); Endantadine (CA); Enzil (TW); Hofcomant (AT, FI); Infectoflu (DE); Influ-A (IL); Mantadan (IT); Mantidan (BR); Paritrel (IL); PK-Merz (AE, AT, BF, BG, BH, BJ, CH, CI, CL, CR, CY, CZ, DE, DO, EG, ET, GH, GM, GN, GT, HK, HU, IL, IQ, IR, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, PA, PK, PT, PY, QA, SA, SC, SD, SL, SN, SY, TW, TZ, UG, YE, ZM, ZW); PMS-Amantadine (CA); Prayanol (CL); Protexin (ES); Symmetrel (AE, AT, AU, BH, CA, CH, CY, DE, EG, GB, GR, HR, IE, IQ, IR, JO, KW, LB, LY, NL, NO, NZ, OM, QA, SA, SY, VE, YE, ZA); Tregor (DE); U.M.T. (DE); Viregyt-K (PL); Virofral (SE); Virosol (AR)
MECHANISM OF ACTION — As an antiviral, blocks the uncoating of influenza A virus preventing penetration of virus into host; antiparkinsonian activity may be due to its blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers
PHARMACODYNAMICS / KINETICS Onset of action: Antidyskinetic: Within 48 hours
Absorption: Well absorbed
Distribution: Vd: Normal: 1.5-6.1 L/kg; Renal failure: 5.1 +/- 0.2 L/kg; in saliva, tear film, and nasal secretions; in animals, tissue (especially lung) concentrations higher than serum concentrations; crosses blood-brain barrier
Protein binding: Normal renal function: ~67%; Hemodialysis: ~59%
Metabolism: Not appreciable; small amounts of an acetyl metabolite identified
Bioavailability: 86% to 90%
Half-life elimination: Normal renal function: 16 +/- 6 hours (9-31 hours); End-stage renal disease: 7-10 days
Excretion: Urine (80% to 90% unchanged) by glomerular filtration and tubular secretion Total clearance: 2.5-10.5 L/hour
PATIENT INFORMATION — Do not abruptly discontinue therapy; it may precipitate a parkinsonian crisis. May impair ability to perform activities requiring mental alertness or coordination. Take throughout flu season or for at least 10 days following vaccination for effective prophylaxis. Take second dose of the day in early afternoon to decrease incidence of insomnia.
The Center for Disease Control (CDC) has made an interim recommendation to the 2005-2006 Influenza Guidelines. Due to increased resistance reported during the beginning of this season, the CDC is recommending that amantadine and rimantadine no longer be used for the treatment or prophylaxis of influenza A in the United States. If an antiviral medication is needed, oseltamivir or zanamivir should be used. Amantadine may still be used for its other approved indications, such as in the treatment of Parkinson's disease.
For additional information, refer to the following CDC website: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm55d117a1.htm?s_cid=mm55d117a1_e
U.S. BRAND NAMES — Symmetrel®
PHARMACOLOGIC CATEGORY Anti-Parkinson's Agent, Dopamine AgonistAntiviral Agent, Adamantane
DOSING: ADULTS Influenza A treatment: Oral: 100 mg twice daily; initiate within 24-48 hours after onset of symptoms; discontinue as soon as possible based on clinical response (generally within 3-5 days or within 24-48 hours after symptoms disappear).
Influenza A prophylaxis: Oral: 100 mg twice daily; continue treatment throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.
Drug-induced extrapyramidal symptoms: Oral: 100 mg twice daily; may increase to 300-400 mg/day, if needed
Parkinson's disease or Creutzfeldt-Jakob disease (unlabeled use): Oral: 100 mg twice daily as sole therapy; may increase to 400 mg/day if needed with close monitoring; initial dose: 100 mg/day if with other serious illness or with high doses of other anti-Parkinson drugs
DOSING: PEDIATRIC
(For additional information see "Amantadine: Pediatric drug information")Influenza A treatment: Oral: Note: Initiate within 24-48 hours after onset of symptoms; discontinue as soon as possible based on clinical response (generally within 3-5 days or within 24-48 hours after symptoms disappear) 1-9 years: 5 mg/kg/day in 2 divided doses (manufacturers range: 4.4-8.8 mg/kg/day); maximum dose: 150 mg/day 10 years and <40 kg: 5 mg/kg/day; maximum dose: 150 mg/day 10 years and 40 kg: Refer to adult dosing.
Influenza A prophylaxis: Oral: Refer to "Influenza A treatment" dosing. Continue treatment throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed. For children <9 years receiving influenza vaccine for the first time, amantadine prophylaxis should continue for 6 weeks (4 weeks after the first dose and 2 weeks after the second dose)
DOSING: ELDERLY — Adjust dose based on renal function; some patients tolerate the drug better when it is given in 2 divided daily doses (to avoid adverse neurologic reactions).
Influenza A prophylaxis or treatment: 100 mg/day in patients 65 years
DOSING: RENAL IMPAIRMENT Clcr 30-50 mL/minute: Administer 200 mg on day 1, then 100 mg/day
Clcr 15-29 mL/minute: Administer 200 mg on day 1, then 100 mg on alternate days
Clcr <15 mL/minute: Administer 200 mg every 7 days
Hemodialysis: Administer 200 mg every 7 days
Peritoneal dialysis: No supplemental dose is needed
Continuous arteriovenous or venous-venous hemofiltration: No supplemental dose is needed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 100 mg
Syrup, as hydrochloride: 50 mg/5 mL (480 mL)
Tablet, as hydrochloride: 100 mg Symmetrel®: 100 mg
DOSAGE FORMS: CONCISE Capsule: 100 mg
Syrup: 50 mg/5 mL
Tablet: 100 mg Symmetrel®: 100 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Prophylaxis and treatment of influenza A viral infection (per manufacturer labeling; also refer to current CDC guidelines for recommendations during current flu season); treatment of parkinsonism; treatment of drug-induced extrapyramidal symptoms
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Cardiovascular: Orthostatic hypotension, peripheral edema Central nervous system: Agitation, anxiety, ataxia, confusion, delirium, depression, dizziness, dream abnormality, fatigue, hallucinations, headache, insomnia, irritability, nervousness, somnolence Dermatologic: Livedo reticularis Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia Respiratory: Dry nose
<1% (Limited to important or life-threatening): Aggressive behavior, agranulocytosis, allergic reaction, amnesia, anaphylaxis, arrhythmia, cardiac arrest, CHF, coma, delirium, delusions, diaphoresis, dysphagia, dyspnea, eczematoid dermatitis, euphoria, hyperkinesis, leukopenia, mania, neutropenia, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), oculogyric episodes, paresthesia, photosensitivity, psychosis, pulmonary edema, rash, respiratory failure (acute), seizures, suicidal ideation, suicide, urinary retention, withdrawal reactions (may include delirium, hallucinations, and psychosis), visual disturbances
CONTRAINDICATIONS — Hypersensitivity to amantadine, rimantadine, or any component of the formulation
WARNINGS / PRECAUTIONS — Use with caution in patients with liver disease, history of recurrent and eczematoid dermatitis, uncontrolled psychosis or severe psychoneurosis, seizures, and in those receiving CNS-stimulant drugs; reduce dose in renal disease. When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months. Elderly patients may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation). Has not been shown to prevent bacterial infection or complications when used as prophylaxis or treatment of influenza A. Use with caution in patients with CHF, peripheral edema, or orthostatic hypotension. Avoid in untreated angle closure glaucoma. Due to increased resistance, in June 2006, the CDC recommended that amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established.
DRUG INTERACTIONS Anticholinergics may potentiate CNS side effects of amantadine; monitor for altered response; includes benztropine and trihexyphenidyl, as well as agents with anticholinergic activity (eg, quinidine, tricyclics, and antihistamines).
Antipsychotics (typical): May reduce the anti-Parkinsonian effects of amantadine
Triamterene: Has been reported to increase the potential for toxicity with amantadine (limited documentation); monitor response.
Vaccine: Influenza (live, attenuated): The live, attenuated form of influenza vaccine (administered intranasally) should not be administered within 2 weeks before or 48 hours after amantadine (unless medically indicated). Inactivated vaccine (trivalent) may be administered without concern to patients receiving amantadine.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase CNS adverse effects).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were observed in animal studies; limited data in humans. Impaired fertility has also been reported during animal studies and during human in vitro fertilization.
LACTATION — Enters breast milk/not recommended
PRICING — (data from drugstore.com)Syrup (Amantadine HCl) 50 mg/5 mL (120): $15.99
Syrup (Symmetrel) 50 mg/5 mL (120): $36.23
Tablets (Symmetrel) 100 mg (60): $82.09
MONITORING PARAMETERS — Renal function, Parkinson's symptoms, mental status, influenza symptoms, blood pressure
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose are generally consistent with excessive anticholinergic effects and include nausea, vomiting, slurred speech, blurred vision, lethargy, hallucinations, seizures, myoclonic jerking, and ventricular arrhythmias. Acute toxicity may be primarily due to anticholinergic effects. The minimum lethal dose may be as low as 1 g. Treatment should be supportive and directed at reducing CNS stimulation, controlling seizures, and maintaining cardiovascular function.
CANADIAN BRAND NAMES — Endantadine®; PMS-Amantadine; Symmetrel®
INTERNATIONAL BRAND NAMES — a.m.t. (DE); Amanda (TW); Amandin (TW); Amandine (UY); Amantadin (EE); Amantadin-ratiopharm (PL); Amantan (BE); Amantix (CO, PL); Amantrel (IN); Amazolon (JP); Atarin (FI); Boidan (JP); Endantadine (CA); Enzil (TW); Hofcomant (AT, FI); Infectoflu (DE); Influ-A (IL); Mantadan (IT); Mantidan (BR); Paritrel (IL); PK-Merz (AE, AT, BF, BG, BH, BJ, CH, CI, CL, CR, CY, CZ, DE, DO, EG, ET, GH, GM, GN, GT, HK, HU, IL, IQ, IR, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, PA, PK, PT, PY, QA, SA, SC, SD, SL, SN, SY, TW, TZ, UG, YE, ZM, ZW); PMS-Amantadine (CA); Prayanol (CL); Protexin (ES); Symmetrel (AE, AT, AU, BH, CA, CH, CY, DE, EG, GB, GR, HR, IE, IQ, IR, JO, KW, LB, LY, NL, NO, NZ, OM, QA, SA, SY, VE, YE, ZA); Tregor (DE); U.M.T. (DE); Viregyt-K (PL); Virofral (SE); Virosol (AR)
MECHANISM OF ACTION — As an antiviral, blocks the uncoating of influenza A virus preventing penetration of virus into host; antiparkinsonian activity may be due to its blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers
PHARMACODYNAMICS / KINETICS Onset of action: Antidyskinetic: Within 48 hours
Absorption: Well absorbed
Distribution: Vd: Normal: 1.5-6.1 L/kg; Renal failure: 5.1 +/- 0.2 L/kg; in saliva, tear film, and nasal secretions; in animals, tissue (especially lung) concentrations higher than serum concentrations; crosses blood-brain barrier
Protein binding: Normal renal function: ~67%; Hemodialysis: ~59%
Metabolism: Not appreciable; small amounts of an acetyl metabolite identified
Bioavailability: 86% to 90%
Half-life elimination: Normal renal function: 16 +/- 6 hours (9-31 hours); End-stage renal disease: 7-10 days
Excretion: Urine (80% to 90% unchanged) by glomerular filtration and tubular secretion Total clearance: 2.5-10.5 L/hour
PATIENT INFORMATION — Do not abruptly discontinue therapy; it may precipitate a parkinsonian crisis. May impair ability to perform activities requiring mental alertness or coordination. Take throughout flu season or for at least 10 days following vaccination for effective prophylaxis. Take second dose of the day in early afternoon to decrease incidence of insomnia.
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