U.S. BRAND NAMES — Soriatane® CK Convenience Kit™
PHARMACOLOGIC CATEGORY
Retinoid-Like Compound
DOSING: ADULTS
Psoriasis: Oral: Individualization of dosage is required to achieve maximum therapeutic response while minimizing side effects
Initial therapy: Therapy should be initiated at 25-50 mg/day, given as a single dose with the main meal
Maintenance: Doses of 25-50 mg/day may be given after initial response to treatment; the maintenance dose should be based on clinical efficacy and tolerability
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:
Soriatane® CK Convenience Kit™ : 10 mg, 25 mg [packaged with VersaFoam-EF™ ]
DOSAGE FORMS: CONCISE
Capsule:
Soriatane® CK Convenience Kit™ : 10 mg, 25 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of severe psoriasis
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Hyperesthesia (10% to 25%)
Dermatologic: Cheilitis (>75%), alopecia (50% to 75%), skin peeling (50% to 75%), dry skin (25% to 50%), nail disorder (25% to 50%), pruritus (25% to 50%), erythematous rash (10% to 25%), skin atrophy (10% to 25%), sticky skin (10% to 25%), paronychia (10% to 25%)
Endocrine & metabolic: Hypercholesterolemia (25% to 50%), hypertriglyceridemia (50% to 75%), HDL decreased (25% to 50%), phosphorus increased (10% to 25%), potassium increased (10% to 25%), sodium increased (10% to 25%), magnesium increased/decreased (10% to 25%), fasting blood sugar increased (25% to 50%), fasting blood sugar decreased (10% to 25%)
Gastrointestinal: Xerostomia (10% to 25%)
Hematologic: Reticulocytes increased (25% to 50%), hematocrit decreased (10% to 25%), hemoglobin decreased (10% to 25%), WBC increased/decreased (10% to 25%), haptoglobin increased (10% to 25%), neutrophils increased (10% to 25%)
Hepatic: Liver function tests increased (25% to 50%), alkaline phosphatase increased (10% to 25%), direct bilirubin increased (10% to 25%), GGTP increased (10% to 25%)
Neuromuscular & skeletal: Paresthesia (10% to 25%), arthralgia (10% to 25%), rigors (10% to 25%), CPK increased (25% to 50%), spinal hyperostosis progression (10% to 25%)
Ocular: Xerophthalmia (10% to 25%),
Renal: Uric acid increased (10% to 25%), acetonuria (10% to 25%), hematuria (10% to 25%), RBC in urine (10% to 25%)
Respiratory: Rhinitis (25% to 50%), epistaxis (10% to 25%)
1% to 10%:
Cardiovascular: Flushing, edema
Central nervous system: Headache, pain, depression, insomnia, somnolence, fatigue
Dermatologic: Skin odor, hair texture change, bullous eruption, dermatitis, diaphoresis increased, psoriasiform rash, purpura, pyogenic granuloma, rash, seborrhea, ulcers, fissures, sunburn
Endocrine & metabolic: Hot flashes, potassium decreased, phosphorus decreased, sodium decreased, calcium increased or decreased, chloride increased or decreased
Gastrointestinal: Gingival bleeding, gingivitis, saliva increased, stomatitis, thirst, ulcerative stomatitis, abdominal pain, diarrhea, nausea, taste disturbance, anorexia, appetite increased, tongue disorder
Hepatic: Total bilirubin increased
Neuromuscular & skeletal: Arthritis, back pain, hypertonia, myalgia, osteodynia, peripheral joint hyperostosis, Bell's palsy
Ocular: Blurred vision, blepharitis, conjunctivitis, night blindness, photophobia, corneal epithelial abnormality, eye pain, eyebrow or eyelash loss, diplopia, cataract
Otic: Earache, tinnitus
Renal: BUN increased, creatinine increased, glycosuria, proteinuria
Respiratory: Sinusitis
<1% (Limited to important or life-threatening): Anxiety, bleeding time increased, chest pain, cirrhosis, conjunctival hemorrhage, constipation, corneal ulceration, cyanosis, deafness, diplopia, dizziness, dyspepsia, dysphonia, dysuria, eczema, esophagitis, fever, furunculosis, gastritis, glossitis, gum hyperplasia, hair discoloration, healing impaired, hemorrhage, hepatic dysfunction, hepatitis, hyperkeratosis, hypertrichosis, hypoesthesia, intermittent claudication, itchy eyes, jaundice, leukorrhea, malaise, melena, MI, moniliasis, myopathy, nervousness, neuritis, pancreatitis, papilledema, peripheral ischemia, photosensitivity, pseudotumor cerebri, scleroderma, skin fragility or thinning, spinal hyperostosis (new lesion), stroke, taste loss, tendonitis, thromboembolism
CONTRAINDICATIONS — Hypersensitivity to acitretin, other retinoids, or any component of the formulation; patients who are pregnant or intend on becoming pregnant; ethanol ingestion; severe hepatic or renal dysfunction; chronically-elevated blood lipid levels; concomitant use with methotrexate or tetracyclines
Acitretin is contraindicated in females of childbearing potential unless all of the following conditions apply.
1) Patient has severe psoriasis unresponsive to other therapy or if clinical condition contraindicates other treatments.
2) Patient must have two negative urine or serum pregnancy tests prior to therapy.
3) Patient must have pregnancy test repeated monthly during therapy. After discontinuation of therapy, a pregnancy test must be repeated every 3 months for at least 3 years.
4) Patient must commit to using two effective forms of birth control starting 1 month prior to acitretin treatment and for 3 years after discontinuation. Prescriber must counsel patient about contraception every month during therapy and every 3 months following discontinuation for at least 3 years.
5) Patient is reliable in understanding and carrying out instructions.
6) Patient has received, and acknowledged, understanding of a careful oral and printed explanation of the hazards of fetal exposure to acitretin and the risk of possible contraception failure; this explanation may include showing a line drawing to the patient of an infant with the characteristic external deformities resulting from retinoid exposure during pregnancy. Patient must sign an agreement/informed consent document stating that she understands these risks and that she should not consume ethanol during therapy or for 2 months after discontinuation.
7) All patients (male and female) should not donate blood during and for 3 years following treatment with acitretin.
WARNINGS / PRECAUTIONS
Boxed warnings: Blood donation: See "Other warnings/precautions" below. Ethanol use: See "Concurrent drug therapy issues" below. Hepatotoxicity: See "Concerns related to adverse effects" below. Medication guide: See "Other warnings/precautions" below. Pregnancy/Do Your P.A.R.T. program: See "Special populations" below.
Concerns related to adverse effects: Depression: Depression, including thoughts of self-harm have been reported; use with caution in patients with a history of mental illness. Hepatotoxicity: [U.S. Boxed Warning]: Changes in transaminases occur in up to1/3of patients. Monitor for hepatotoxicity; discontinue if significant elevations of liver enzymes occur. Use with caution in patients at risk of hypertriglyceridemias. Hyperostosis: Patients receiving long-term treatment should be periodically examined for bony abnormalities; if occur risk vs. benefit of therapy should be considered. Lipid effects: Lipid changes including, increased triglycerides, increased cholesterol, and decreased HDL are common (up to 66%); increased triglycerides may lead to pancreatitis. Photosensitivity: May be photosensitizing; minimize sun or other UV exposure to treated areas. Pseudotumor cerebri: Rarely associated with pseudotumor cerebri. Visual disturbances: May cause a decrease in night vision or decreased tolerance to contact lenses; discontinue if visual changes occur.
Concurrent drug therapy issues: Ethanol use: [U.S. Boxed Warning]: All patients (male and female) should abstain from ethanol or ethanol-containing products during therapy and for 2 months after discontinuation. Tetracyclines: Pseudotumor cerebri (benign intracranial hypertension) has been reported with use of tetracyclines and acitretin independently; concomitant use is contraindicated.
Special populations: Pediatrics: Safety and efficacy have not been established in children; growth potential may be affected. Pregnancy/Do Your P.A.R.T. program: [U.S. Boxed Warning]: Not for use by women who are pregnant or want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation. The Do Your P.A.R.T. (Pregnancy Prevention Actively Required During and After Treatment) program explains teratogenic risks and requirements expected of females of childbearing potential to prevent pregnancies from occurring during use and 3 years following discontinuation; this should be used to educate patients and healthcare providers.
Other warnings/precautions: Blood donation: [U.S. Boxed Warning]: All patients should be advised not to donate blood during therapy or for 3 years following completion of therapy. Medication guide: [U.S. Boxed Warning]: All patients must be provided with a medication guide each time acitretin is dispensed. Female patients must also sign an informed consent prior to therapy.
DRUG INTERACTIONS
Alcohol (Ethyl): May enhance the teratogenic effect of Acitretin. Risk X: Avoid combination
Contraceptive (Progestins): Acitretin may diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk X: Avoid combination
Methotrexate: Acitretin may enhance the hepatotoxic effect of Methotrexate. Risk X: Avoid combination
Oral Contraceptive (Estrogens): Retinoic Acid Derivatives may diminish the therapeutic effect of Oral Contraceptive (Estrogens). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Risk C: Monitor therapy
Oral Contraceptive (Progestins): Retinoic Acid Derivatives may diminish the therapeutic effect of Oral Contraceptive (Progestins). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Risk C: Monitor therapy
Tetracycline Derivatives: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Risk X: Avoid combination
Vitamin A: Retinoic Acid Derivatives may enhance the adverse/toxic effect of Vitamin A. Risk X: Avoid combination
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Use leads to formation of etretinate, a teratogenic metabolite with a prolonged half-life; concomitant use of ethanol or ethanol-containing products is contraindicated.
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — Acitretin is teratogenic in humans. Severe birth defects have been reported when conception occurred during treatment or after therapy was complete. [U.S. Boxed Warning]: Not for use by women who want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation. In addition, because ethanol forms a teratogenic metabolite and would increase the duration of teratogenic potential, ethanol should not be consumed during treatment or for 2 months after discontinuation. Limited amounts of acitretin are found in seminal fluid; although it appears this poses little risk to a fetus, the actual risk of teratogenicity is not known. Any pregnancy which occurs during treatment, or within 3 years after treatment is discontinued, should be reported to the manufacturer at 1-888-500-3376 or to the FDA at 1-800-FDA-1088.
LACTATION — Enters breast milk/not recommended
BREAST-FEEDING CONSIDERATIONS — Acitretin should not be given prior to or during nursing due to the potential for adverse effects in the nursing infant.
DIETARY CONSIDERATIONS — Administer with food. Avoid ingestion of additional sources of exogenous vitamin A (in excess of RDA); use of ethanol and ethanol-containing products is contraindicated.
MONITORING PARAMETERS — Lipid profile (baseline and at 1- to 2-week intervals for 4-8 weeks); liver function tests (baseline, and at 1- to 2-week intervals until stable, then as clinically indicated); blood glucose in patients with diabetes; bone abnormalities (with long-term use)
CANADIAN BRAND NAMES — Soriatane®
INTERNATIONAL BRAND NAMES — Acetec (IN); Neo-Tigason (TH); Neotigason (AR, AT, AU, BB, BE, BF, BG, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CZ, DE, DK, EC, EE, EG, ET, FI, GB, GH, GM, GN, GR, GY, HN, IE, IL, IT, JM, KE, KP, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, PE, PH, PL, PT, PY, SC, SD, SE, SL, SN, SR, TN, TT, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Soriatane (FR)
PHARMACODYNAMICS / KINETICS — Etretinate has been detected in serum for up to 3 years following therapy, possibly due to storage in adipose tissue.
Onset of action: May take 2-3 months for full effect; improvement may be seen within 8 weeks.
Absorption: Oral: ~72% absorbed when given with food
Protein binding: >99% bound, primarily to albumin
Metabolism: Metabolized to cis-acitretin; both compounds are further metabolized. Concomitant ethanol use leads to the formation of etretinate (active).
Half-life elimination: Acitretin: 49 hours (range: 33-96); cis-acitretin: 63 hours (range: 28-157); etretinate: 120 days (range: 84-168 days)
Excretion: Feces (34% to 54%); urine (16% to 53%)
PATIENT INFORMATION — Take with food. Do not drink alcohol during therapy and for 2 months after discontinuation. Use contraception for 1 month before, during, and for 3 years after discontinuation. You may not be able to tolerate contact lenses during treatment. Do not donate blood during treatment and for 3 years after discontinuation (male and female patients). Avoid exposure to sunlight. Wear protective clothing and sunscreens. Avoid use of other vitamin A products. Females: Use two effective forms of birth control. If you have had your tubes tied, then use an additional form of birth control. If you become pregnant, contact your prescriber immediately.
Tuesday, May 18, 2010
Acitretin
U.S. BRAND NAMES — Soriatane® CK Convenience Kit™
PHARMACOLOGIC CATEGORY
Retinoid-Like Compound
DOSING: ADULTS
Psoriasis: Oral: Individualization of dosage is required to achieve maximum therapeutic response while minimizing side effects
Initial therapy: Therapy should be initiated at 25-50 mg/day, given as a single dose with the main meal
Maintenance: Doses of 25-50 mg/day may be given after initial response to treatment; the maintenance dose should be based on clinical efficacy and tolerability
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:
Soriatane® CK Convenience Kit™ : 10 mg, 25 mg [packaged with VersaFoam-EF™ ]
DOSAGE FORMS: CONCISE
Capsule:
Soriatane® CK Convenience Kit™ : 10 mg, 25 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of severe psoriasis
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Hyperesthesia (10% to 25%)
Dermatologic: Cheilitis (>75%), alopecia (50% to 75%), skin peeling (50% to 75%), dry skin (25% to 50%), nail disorder (25% to 50%), pruritus (25% to 50%), erythematous rash (10% to 25%), skin atrophy (10% to 25%), sticky skin (10% to 25%), paronychia (10% to 25%)
Endocrine & metabolic: Hypercholesterolemia (25% to 50%), hypertriglyceridemia (50% to 75%), HDL decreased (25% to 50%), phosphorus increased (10% to 25%), potassium increased (10% to 25%), sodium increased (10% to 25%), magnesium increased/decreased (10% to 25%), fasting blood sugar increased (25% to 50%), fasting blood sugar decreased (10% to 25%)
Gastrointestinal: Xerostomia (10% to 25%)
Hematologic: Reticulocytes increased (25% to 50%), hematocrit decreased (10% to 25%), hemoglobin decreased (10% to 25%), WBC increased/decreased (10% to 25%), haptoglobin increased (10% to 25%), neutrophils increased (10% to 25%)
Hepatic: Liver function tests increased (25% to 50%), alkaline phosphatase increased (10% to 25%), direct bilirubin increased (10% to 25%), GGTP increased (10% to 25%)
Neuromuscular & skeletal: Paresthesia (10% to 25%), arthralgia (10% to 25%), rigors (10% to 25%), CPK increased (25% to 50%), spinal hyperostosis progression (10% to 25%)
Ocular: Xerophthalmia (10% to 25%),
Renal: Uric acid increased (10% to 25%), acetonuria (10% to 25%), hematuria (10% to 25%), RBC in urine (10% to 25%)
Respiratory: Rhinitis (25% to 50%), epistaxis (10% to 25%)
1% to 10%:
Cardiovascular: Flushing, edema
Central nervous system: Headache, pain, depression, insomnia, somnolence, fatigue
Dermatologic: Skin odor, hair texture change, bullous eruption, dermatitis, diaphoresis increased, psoriasiform rash, purpura, pyogenic granuloma, rash, seborrhea, ulcers, fissures, sunburn
Endocrine & metabolic: Hot flashes, potassium decreased, phosphorus decreased, sodium decreased, calcium increased or decreased, chloride increased or decreased
Gastrointestinal: Gingival bleeding, gingivitis, saliva increased, stomatitis, thirst, ulcerative stomatitis, abdominal pain, diarrhea, nausea, taste disturbance, anorexia, appetite increased, tongue disorder
Hepatic: Total bilirubin increased
Neuromuscular & skeletal: Arthritis, back pain, hypertonia, myalgia, osteodynia, peripheral joint hyperostosis, Bell's palsy
Ocular: Blurred vision, blepharitis, conjunctivitis, night blindness, photophobia, corneal epithelial abnormality, eye pain, eyebrow or eyelash loss, diplopia, cataract
Otic: Earache, tinnitus
Renal: BUN increased, creatinine increased, glycosuria, proteinuria
Respiratory: Sinusitis
<1% (Limited to important or life-threatening): Anxiety, bleeding time increased, chest pain, cirrhosis, conjunctival hemorrhage, constipation, corneal ulceration, cyanosis, deafness, diplopia, dizziness, dyspepsia, dysphonia, dysuria, eczema, esophagitis, fever, furunculosis, gastritis, glossitis, gum hyperplasia, hair discoloration, healing impaired, hemorrhage, hepatic dysfunction, hepatitis, hyperkeratosis, hypertrichosis, hypoesthesia, intermittent claudication, itchy eyes, jaundice, leukorrhea, malaise, melena, MI, moniliasis, myopathy, nervousness, neuritis, pancreatitis, papilledema, peripheral ischemia, photosensitivity, pseudotumor cerebri, scleroderma, skin fragility or thinning, spinal hyperostosis (new lesion), stroke, taste loss, tendonitis, thromboembolism
CONTRAINDICATIONS — Hypersensitivity to acitretin, other retinoids, or any component of the formulation; patients who are pregnant or intend on becoming pregnant; ethanol ingestion; severe hepatic or renal dysfunction; chronically-elevated blood lipid levels; concomitant use with methotrexate or tetracyclines
Acitretin is contraindicated in females of childbearing potential unless all of the following conditions apply.
1) Patient has severe psoriasis unresponsive to other therapy or if clinical condition contraindicates other treatments.
2) Patient must have two negative urine or serum pregnancy tests prior to therapy.
3) Patient must have pregnancy test repeated monthly during therapy. After discontinuation of therapy, a pregnancy test must be repeated every 3 months for at least 3 years.
4) Patient must commit to using two effective forms of birth control starting 1 month prior to acitretin treatment and for 3 years after discontinuation. Prescriber must counsel patient about contraception every month during therapy and every 3 months following discontinuation for at least 3 years.
5) Patient is reliable in understanding and carrying out instructions.
6) Patient has received, and acknowledged, understanding of a careful oral and printed explanation of the hazards of fetal exposure to acitretin and the risk of possible contraception failure; this explanation may include showing a line drawing to the patient of an infant with the characteristic external deformities resulting from retinoid exposure during pregnancy. Patient must sign an agreement/informed consent document stating that she understands these risks and that she should not consume ethanol during therapy or for 2 months after discontinuation.
7) All patients (male and female) should not donate blood during and for 3 years following treatment with acitretin.
WARNINGS / PRECAUTIONS
Boxed warnings: Blood donation: See "Other warnings/precautions" below. Ethanol use: See "Concurrent drug therapy issues" below. Hepatotoxicity: See "Concerns related to adverse effects" below. Medication guide: See "Other warnings/precautions" below. Pregnancy/Do Your P.A.R.T. program: See "Special populations" below.
Concerns related to adverse effects: Depression: Depression, including thoughts of self-harm have been reported; use with caution in patients with a history of mental illness. Hepatotoxicity: [U.S. Boxed Warning]: Changes in transaminases occur in up to1/3of patients. Monitor for hepatotoxicity; discontinue if significant elevations of liver enzymes occur. Use with caution in patients at risk of hypertriglyceridemias. Hyperostosis: Patients receiving long-term treatment should be periodically examined for bony abnormalities; if occur risk vs. benefit of therapy should be considered. Lipid effects: Lipid changes including, increased triglycerides, increased cholesterol, and decreased HDL are common (up to 66%); increased triglycerides may lead to pancreatitis. Photosensitivity: May be photosensitizing; minimize sun or other UV exposure to treated areas. Pseudotumor cerebri: Rarely associated with pseudotumor cerebri. Visual disturbances: May cause a decrease in night vision or decreased tolerance to contact lenses; discontinue if visual changes occur.
Concurrent drug therapy issues: Ethanol use: [U.S. Boxed Warning]: All patients (male and female) should abstain from ethanol or ethanol-containing products during therapy and for 2 months after discontinuation. Tetracyclines: Pseudotumor cerebri (benign intracranial hypertension) has been reported with use of tetracyclines and acitretin independently; concomitant use is contraindicated.
Special populations: Pediatrics: Safety and efficacy have not been established in children; growth potential may be affected. Pregnancy/Do Your P.A.R.T. program: [U.S. Boxed Warning]: Not for use by women who are pregnant or want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation. The Do Your P.A.R.T. (Pregnancy Prevention Actively Required During and After Treatment) program explains teratogenic risks and requirements expected of females of childbearing potential to prevent pregnancies from occurring during use and 3 years following discontinuation; this should be used to educate patients and healthcare providers.
Other warnings/precautions: Blood donation: [U.S. Boxed Warning]: All patients should be advised not to donate blood during therapy or for 3 years following completion of therapy. Medication guide: [U.S. Boxed Warning]: All patients must be provided with a medication guide each time acitretin is dispensed. Female patients must also sign an informed consent prior to therapy.
DRUG INTERACTIONS
Alcohol (Ethyl): May enhance the teratogenic effect of Acitretin. Risk X: Avoid combination
Contraceptive (Progestins): Acitretin may diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk X: Avoid combination
Methotrexate: Acitretin may enhance the hepatotoxic effect of Methotrexate. Risk X: Avoid combination
Oral Contraceptive (Estrogens): Retinoic Acid Derivatives may diminish the therapeutic effect of Oral Contraceptive (Estrogens). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Risk C: Monitor therapy
Oral Contraceptive (Progestins): Retinoic Acid Derivatives may diminish the therapeutic effect of Oral Contraceptive (Progestins). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Risk C: Monitor therapy
Tetracycline Derivatives: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Risk X: Avoid combination
Vitamin A: Retinoic Acid Derivatives may enhance the adverse/toxic effect of Vitamin A. Risk X: Avoid combination
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Use leads to formation of etretinate, a teratogenic metabolite with a prolonged half-life; concomitant use of ethanol or ethanol-containing products is contraindicated.
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — Acitretin is teratogenic in humans. Severe birth defects have been reported when conception occurred during treatment or after therapy was complete. [U.S. Boxed Warning]: Not for use by women who want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation. In addition, because ethanol forms a teratogenic metabolite and would increase the duration of teratogenic potential, ethanol should not be consumed during treatment or for 2 months after discontinuation. Limited amounts of acitretin are found in seminal fluid; although it appears this poses little risk to a fetus, the actual risk of teratogenicity is not known. Any pregnancy which occurs during treatment, or within 3 years after treatment is discontinued, should be reported to the manufacturer at 1-888-500-3376 or to the FDA at 1-800-FDA-1088.
LACTATION — Enters breast milk/not recommended
BREAST-FEEDING CONSIDERATIONS — Acitretin should not be given prior to or during nursing due to the potential for adverse effects in the nursing infant.
DIETARY CONSIDERATIONS — Administer with food. Avoid ingestion of additional sources of exogenous vitamin A (in excess of RDA); use of ethanol and ethanol-containing products is contraindicated.
MONITORING PARAMETERS — Lipid profile (baseline and at 1- to 2-week intervals for 4-8 weeks); liver function tests (baseline, and at 1- to 2-week intervals until stable, then as clinically indicated); blood glucose in patients with diabetes; bone abnormalities (with long-term use)
CANADIAN BRAND NAMES — Soriatane®
INTERNATIONAL BRAND NAMES — Acetec (IN); Neo-Tigason (TH); Neotigason (AR, AT, AU, BB, BE, BF, BG, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CZ, DE, DK, EC, EE, EG, ET, FI, GB, GH, GM, GN, GR, GY, HN, IE, IL, IT, JM, KE, KP, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, PE, PH, PL, PT, PY, SC, SD, SE, SL, SN, SR, TN, TT, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Soriatane (FR)
PHARMACODYNAMICS / KINETICS — Etretinate has been detected in serum for up to 3 years following therapy, possibly due to storage in adipose tissue.
Onset of action: May take 2-3 months for full effect; improvement may be seen within 8 weeks.
Absorption: Oral: ~72% absorbed when given with food
Protein binding: >99% bound, primarily to albumin
Metabolism: Metabolized to cis-acitretin; both compounds are further metabolized. Concomitant ethanol use leads to the formation of etretinate (active).
Half-life elimination: Acitretin: 49 hours (range: 33-96); cis-acitretin: 63 hours (range: 28-157); etretinate: 120 days (range: 84-168 days)
Excretion: Feces (34% to 54%); urine (16% to 53%)
PATIENT INFORMATION — Take with food. Do not drink alcohol during therapy and for 2 months after discontinuation. Use contraception for 1 month before, during, and for 3 years after discontinuation. You may not be able to tolerate contact lenses during treatment. Do not donate blood during treatment and for 3 years after discontinuation (male and female patients). Avoid exposure to sunlight. Wear protective clothing and sunscreens. Avoid use of other vitamin A products. Females: Use two effective forms of birth control. If you have had your tubes tied, then use an additional form of birth control. If you become pregnant, contact your prescriber immediately.
PHARMACOLOGIC CATEGORY
Retinoid-Like Compound
DOSING: ADULTS
Psoriasis: Oral: Individualization of dosage is required to achieve maximum therapeutic response while minimizing side effects
Initial therapy: Therapy should be initiated at 25-50 mg/day, given as a single dose with the main meal
Maintenance: Doses of 25-50 mg/day may be given after initial response to treatment; the maintenance dose should be based on clinical efficacy and tolerability
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:
Soriatane® CK Convenience Kit™ : 10 mg, 25 mg [packaged with VersaFoam-EF™ ]
DOSAGE FORMS: CONCISE
Capsule:
Soriatane® CK Convenience Kit™ : 10 mg, 25 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of severe psoriasis
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Hyperesthesia (10% to 25%)
Dermatologic: Cheilitis (>75%), alopecia (50% to 75%), skin peeling (50% to 75%), dry skin (25% to 50%), nail disorder (25% to 50%), pruritus (25% to 50%), erythematous rash (10% to 25%), skin atrophy (10% to 25%), sticky skin (10% to 25%), paronychia (10% to 25%)
Endocrine & metabolic: Hypercholesterolemia (25% to 50%), hypertriglyceridemia (50% to 75%), HDL decreased (25% to 50%), phosphorus increased (10% to 25%), potassium increased (10% to 25%), sodium increased (10% to 25%), magnesium increased/decreased (10% to 25%), fasting blood sugar increased (25% to 50%), fasting blood sugar decreased (10% to 25%)
Gastrointestinal: Xerostomia (10% to 25%)
Hematologic: Reticulocytes increased (25% to 50%), hematocrit decreased (10% to 25%), hemoglobin decreased (10% to 25%), WBC increased/decreased (10% to 25%), haptoglobin increased (10% to 25%), neutrophils increased (10% to 25%)
Hepatic: Liver function tests increased (25% to 50%), alkaline phosphatase increased (10% to 25%), direct bilirubin increased (10% to 25%), GGTP increased (10% to 25%)
Neuromuscular & skeletal: Paresthesia (10% to 25%), arthralgia (10% to 25%), rigors (10% to 25%), CPK increased (25% to 50%), spinal hyperostosis progression (10% to 25%)
Ocular: Xerophthalmia (10% to 25%),
Renal: Uric acid increased (10% to 25%), acetonuria (10% to 25%), hematuria (10% to 25%), RBC in urine (10% to 25%)
Respiratory: Rhinitis (25% to 50%), epistaxis (10% to 25%)
1% to 10%:
Cardiovascular: Flushing, edema
Central nervous system: Headache, pain, depression, insomnia, somnolence, fatigue
Dermatologic: Skin odor, hair texture change, bullous eruption, dermatitis, diaphoresis increased, psoriasiform rash, purpura, pyogenic granuloma, rash, seborrhea, ulcers, fissures, sunburn
Endocrine & metabolic: Hot flashes, potassium decreased, phosphorus decreased, sodium decreased, calcium increased or decreased, chloride increased or decreased
Gastrointestinal: Gingival bleeding, gingivitis, saliva increased, stomatitis, thirst, ulcerative stomatitis, abdominal pain, diarrhea, nausea, taste disturbance, anorexia, appetite increased, tongue disorder
Hepatic: Total bilirubin increased
Neuromuscular & skeletal: Arthritis, back pain, hypertonia, myalgia, osteodynia, peripheral joint hyperostosis, Bell's palsy
Ocular: Blurred vision, blepharitis, conjunctivitis, night blindness, photophobia, corneal epithelial abnormality, eye pain, eyebrow or eyelash loss, diplopia, cataract
Otic: Earache, tinnitus
Renal: BUN increased, creatinine increased, glycosuria, proteinuria
Respiratory: Sinusitis
<1% (Limited to important or life-threatening): Anxiety, bleeding time increased, chest pain, cirrhosis, conjunctival hemorrhage, constipation, corneal ulceration, cyanosis, deafness, diplopia, dizziness, dyspepsia, dysphonia, dysuria, eczema, esophagitis, fever, furunculosis, gastritis, glossitis, gum hyperplasia, hair discoloration, healing impaired, hemorrhage, hepatic dysfunction, hepatitis, hyperkeratosis, hypertrichosis, hypoesthesia, intermittent claudication, itchy eyes, jaundice, leukorrhea, malaise, melena, MI, moniliasis, myopathy, nervousness, neuritis, pancreatitis, papilledema, peripheral ischemia, photosensitivity, pseudotumor cerebri, scleroderma, skin fragility or thinning, spinal hyperostosis (new lesion), stroke, taste loss, tendonitis, thromboembolism
CONTRAINDICATIONS — Hypersensitivity to acitretin, other retinoids, or any component of the formulation; patients who are pregnant or intend on becoming pregnant; ethanol ingestion; severe hepatic or renal dysfunction; chronically-elevated blood lipid levels; concomitant use with methotrexate or tetracyclines
Acitretin is contraindicated in females of childbearing potential unless all of the following conditions apply.
1) Patient has severe psoriasis unresponsive to other therapy or if clinical condition contraindicates other treatments.
2) Patient must have two negative urine or serum pregnancy tests prior to therapy.
3) Patient must have pregnancy test repeated monthly during therapy. After discontinuation of therapy, a pregnancy test must be repeated every 3 months for at least 3 years.
4) Patient must commit to using two effective forms of birth control starting 1 month prior to acitretin treatment and for 3 years after discontinuation. Prescriber must counsel patient about contraception every month during therapy and every 3 months following discontinuation for at least 3 years.
5) Patient is reliable in understanding and carrying out instructions.
6) Patient has received, and acknowledged, understanding of a careful oral and printed explanation of the hazards of fetal exposure to acitretin and the risk of possible contraception failure; this explanation may include showing a line drawing to the patient of an infant with the characteristic external deformities resulting from retinoid exposure during pregnancy. Patient must sign an agreement/informed consent document stating that she understands these risks and that she should not consume ethanol during therapy or for 2 months after discontinuation.
7) All patients (male and female) should not donate blood during and for 3 years following treatment with acitretin.
WARNINGS / PRECAUTIONS
Boxed warnings: Blood donation: See "Other warnings/precautions" below. Ethanol use: See "Concurrent drug therapy issues" below. Hepatotoxicity: See "Concerns related to adverse effects" below. Medication guide: See "Other warnings/precautions" below. Pregnancy/Do Your P.A.R.T. program: See "Special populations" below.
Concerns related to adverse effects: Depression: Depression, including thoughts of self-harm have been reported; use with caution in patients with a history of mental illness. Hepatotoxicity: [U.S. Boxed Warning]: Changes in transaminases occur in up to1/3of patients. Monitor for hepatotoxicity; discontinue if significant elevations of liver enzymes occur. Use with caution in patients at risk of hypertriglyceridemias. Hyperostosis: Patients receiving long-term treatment should be periodically examined for bony abnormalities; if occur risk vs. benefit of therapy should be considered. Lipid effects: Lipid changes including, increased triglycerides, increased cholesterol, and decreased HDL are common (up to 66%); increased triglycerides may lead to pancreatitis. Photosensitivity: May be photosensitizing; minimize sun or other UV exposure to treated areas. Pseudotumor cerebri: Rarely associated with pseudotumor cerebri. Visual disturbances: May cause a decrease in night vision or decreased tolerance to contact lenses; discontinue if visual changes occur.
Concurrent drug therapy issues: Ethanol use: [U.S. Boxed Warning]: All patients (male and female) should abstain from ethanol or ethanol-containing products during therapy and for 2 months after discontinuation. Tetracyclines: Pseudotumor cerebri (benign intracranial hypertension) has been reported with use of tetracyclines and acitretin independently; concomitant use is contraindicated.
Special populations: Pediatrics: Safety and efficacy have not been established in children; growth potential may be affected. Pregnancy/Do Your P.A.R.T. program: [U.S. Boxed Warning]: Not for use by women who are pregnant or want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation. The Do Your P.A.R.T. (Pregnancy Prevention Actively Required During and After Treatment) program explains teratogenic risks and requirements expected of females of childbearing potential to prevent pregnancies from occurring during use and 3 years following discontinuation; this should be used to educate patients and healthcare providers.
Other warnings/precautions: Blood donation: [U.S. Boxed Warning]: All patients should be advised not to donate blood during therapy or for 3 years following completion of therapy. Medication guide: [U.S. Boxed Warning]: All patients must be provided with a medication guide each time acitretin is dispensed. Female patients must also sign an informed consent prior to therapy.
DRUG INTERACTIONS
Alcohol (Ethyl): May enhance the teratogenic effect of Acitretin. Risk X: Avoid combination
Contraceptive (Progestins): Acitretin may diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk X: Avoid combination
Methotrexate: Acitretin may enhance the hepatotoxic effect of Methotrexate. Risk X: Avoid combination
Oral Contraceptive (Estrogens): Retinoic Acid Derivatives may diminish the therapeutic effect of Oral Contraceptive (Estrogens). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Risk C: Monitor therapy
Oral Contraceptive (Progestins): Retinoic Acid Derivatives may diminish the therapeutic effect of Oral Contraceptive (Progestins). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Risk C: Monitor therapy
Tetracycline Derivatives: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Risk X: Avoid combination
Vitamin A: Retinoic Acid Derivatives may enhance the adverse/toxic effect of Vitamin A. Risk X: Avoid combination
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Use leads to formation of etretinate, a teratogenic metabolite with a prolonged half-life; concomitant use of ethanol or ethanol-containing products is contraindicated.
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — Acitretin is teratogenic in humans. Severe birth defects have been reported when conception occurred during treatment or after therapy was complete. [U.S. Boxed Warning]: Not for use by women who want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation. In addition, because ethanol forms a teratogenic metabolite and would increase the duration of teratogenic potential, ethanol should not be consumed during treatment or for 2 months after discontinuation. Limited amounts of acitretin are found in seminal fluid; although it appears this poses little risk to a fetus, the actual risk of teratogenicity is not known. Any pregnancy which occurs during treatment, or within 3 years after treatment is discontinued, should be reported to the manufacturer at 1-888-500-3376 or to the FDA at 1-800-FDA-1088.
LACTATION — Enters breast milk/not recommended
BREAST-FEEDING CONSIDERATIONS — Acitretin should not be given prior to or during nursing due to the potential for adverse effects in the nursing infant.
DIETARY CONSIDERATIONS — Administer with food. Avoid ingestion of additional sources of exogenous vitamin A (in excess of RDA); use of ethanol and ethanol-containing products is contraindicated.
MONITORING PARAMETERS — Lipid profile (baseline and at 1- to 2-week intervals for 4-8 weeks); liver function tests (baseline, and at 1- to 2-week intervals until stable, then as clinically indicated); blood glucose in patients with diabetes; bone abnormalities (with long-term use)
CANADIAN BRAND NAMES — Soriatane®
INTERNATIONAL BRAND NAMES — Acetec (IN); Neo-Tigason (TH); Neotigason (AR, AT, AU, BB, BE, BF, BG, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CZ, DE, DK, EC, EE, EG, ET, FI, GB, GH, GM, GN, GR, GY, HN, IE, IL, IT, JM, KE, KP, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, PE, PH, PL, PT, PY, SC, SD, SE, SL, SN, SR, TN, TT, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Soriatane (FR)
PHARMACODYNAMICS / KINETICS — Etretinate has been detected in serum for up to 3 years following therapy, possibly due to storage in adipose tissue.
Onset of action: May take 2-3 months for full effect; improvement may be seen within 8 weeks.
Absorption: Oral: ~72% absorbed when given with food
Protein binding: >99% bound, primarily to albumin
Metabolism: Metabolized to cis-acitretin; both compounds are further metabolized. Concomitant ethanol use leads to the formation of etretinate (active).
Half-life elimination: Acitretin: 49 hours (range: 33-96); cis-acitretin: 63 hours (range: 28-157); etretinate: 120 days (range: 84-168 days)
Excretion: Feces (34% to 54%); urine (16% to 53%)
PATIENT INFORMATION — Take with food. Do not drink alcohol during therapy and for 2 months after discontinuation. Use contraception for 1 month before, during, and for 3 years after discontinuation. You may not be able to tolerate contact lenses during treatment. Do not donate blood during treatment and for 3 years after discontinuation (male and female patients). Avoid exposure to sunlight. Wear protective clothing and sunscreens. Avoid use of other vitamin A products. Females: Use two effective forms of birth control. If you have had your tubes tied, then use an additional form of birth control. If you become pregnant, contact your prescriber immediately.
Acetylcysteine
U.S. BRAND NAMES — Acetadote®
PHARMACOLOGIC CATEGORY
Antidote
Mucolytic Agent
DOSING: ADULTS
Acetaminophen poisoning: Only the 72-hour oral and 21-hour I.V. regimens are FDA-approved. Ideally, in patients with an acute APAP ingestion, treatment should begin within 8 hours of ingestion. In patients who present following RSTI and treatment is deemed appropriate, acetylcysteine should be initiated immediately.
Oral:Note: Consultation with a poison control center or clinical toxicologist is highly recommended when considering the discontinuation of oral acetylcysteine prior to the conclusion of a full 18-dose course of therapy.
72-hour regimen: Consists of 18 doses; total dose delivered: 1330 mg/kg
Loading dose: 140 mg/kg
Maintenance dose: 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration
I.V. (Acetadote®):
21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg
Loading dose: 150 mg/kg infused over 60 minutes
Second dose: 50 mg/kg infused over 4 hours
Third dose: 100 mg/kg infused over 16 hours
Note: The fluid volume should be reduced in patients weighing <40 kg according to the following table:
Acetadote® Dosing / Fluid Volume Guidelines for Patients <40 kg
Body weight 30 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 22.5 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 7.5 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 15 mL in D5W 500 mL
Body weight 25 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 18.75 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 6.25 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 12.5 mL in D5W 500 mL
Body weight 20 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 15 mL in D5W 60 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 5 mL in D5W 140 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 10 mL in D5W 280 mL
Body weight 15 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 11.25 mL in D5W 45 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 3.75 mL in D5W 105 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 7.5 mL in D5W 210 mL
Body weight 10 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 7.5 mL in D5W 30 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 2.5 mL in D5W 70 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 5 mL in D5W 140 mL
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to dose.
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours
Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment
Direct instillation:
Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours
Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter
Diagnostic bronchogram: Nebulization or intratracheal: 1-2 mL of 20% solution or 2-4 mL of 10% solution administered 2-3 times prior to procedure
Prevention of contrast-induced nephropathy (CIN) (unlabeled use): Oral: 600-1200 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules (some centers use solution, diluted in cola beverage or juice)
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use):I.V.: 1200 mg over 5-10 minutes prior to cardiac catheterization, followed by 1200 mg orally twice daily for 48 hours
DOSING: PEDIATRIC
(For additional information see "Acetylcysteine: Pediatric drug information")
Acetaminophen poisoning: Refer to adult dosing.
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted.
Infants: 1-2 mL of 20% solution or 2-4 mL 10% solution until nebulized given 3-4 times/day
Children: Refer to adult dosing.
Inhalation, nebulization (tent, croupette): Children: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL; contains disodium edetate]
Solution, inhalation/oral: 10% (4 mL, 10 mL, 30 mL) [100 mg/mL]; 20% (4 mL, 10 mL, 30 mL) [200 mg/mL]
DOSAGE FORMS: CONCISE
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL]
Solution, inhalation/oral: 10% [100 mg/mL]; 20% [200 mg/mL]
GENERIC EQUIVALENT AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION
Inhalation: Acetylcysteine is incompatible with tetracyclines, erythromycin, amphotericin B, iodized oil, chymotrypsin, trypsin, and hydrogen peroxide. Administer separately. Intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime.
Oral: Treatment of APAP poisoning, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).
I.V. (Acetadote®):
Acetaminophen poisoning:
Loading dose: Dilute in D5W 200 mL; administer over 60 minutes.
Second dose: Dilute in D5W 500 mL; administer over 4 hours.
Third dose: Dilute in D5W 1000 mL; administer over 16 hours.
Note: To avoid fluid overload in patients <40 kg and those requiring fluid restriction, decrease volume of D5W proportionally (see table in dosing section). Discard unused portion.
If the commercial I.V. form is unavailable, the solution for inhalation has been used; each dose should be infused through a 0.2 micron Millipore filter (in-line) over 60 minutes (Yip, 1998); intravenous administration of the solution for inhalation is not USP 797-compliant.
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use): Administer 1200 mg I.V. push over 5-10 minutes prior to contrast administration.
COMPATIBILITY
Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, tetracycline, oxytetracycline, erythromycin.
Intravenous: Compatible with D5W, 1/2NS, SWFI. Incompatible with rubber, metals (particularly iron, copper, and nickel), cefepime, and ceftazidime.
USE — Antidote for acute acetaminophen (APAP) poisoning; repeated supratherapeutic ingestion (RSTI) of APAP; adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies
USE - UNLABELED / INVESTIGATIONAL — Prevention of contrast-induced renal dysfunction (oral, I.V.); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)
ADVERSE REACTIONS SIGNIFICANT
Inhalation: Frequency not defined.
Central nervous system: Drowsiness, chills, fever
Gastrointestinal: Vomiting, nausea, stomatitis
Local: Irritation, stickiness on face following nebulization
Respiratory: Bronchospasm, rhinorrhea, hemoptysis
Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration
Intravenous:
>10%: Miscellaneous: Anaphylactoid reaction (8% to 18%; shorter infusion periods [eg, <60 minutes] associated with increased incidence)
1% to 10%:
Cardiovascular: Flushing (1% to 8%), tachycardia (1% to 4%), edema (1% to 2%)
Dermatologic: Urticaria (6% to 8%), rash (2% to 4%), pruritus (1% to 4%)
Gastrointestinal: Vomiting (2% to 10%), nausea (1% to 6%)
Respiratory: Pharyngitis (≤ 1%), rhinorrhea (≤ 1%), rhonchi (≤ 1%), throat tightness (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylaxis, bronchospasm, chest tightness, cough, dyspnea, hypotension, respiratory distress, stridor, wheezing
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid reactions: Acute flushing and erythema have been reported; usually occurs within 30-60 minutes and may resolve spontaneously. Serious anaphylactoid reactions have also been reported and are more commonly associated with I.V. administration. When used for APAP poisoning, the incidence is reduced when the initial loading dose is administered over 60 minutes. Acetylcysteine infusion may be interrupted until treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactoid reactions should be immediately available. Use caution in patients with asthma or history of bronchospasm as these patients may be at increased risk. Conversely, patients with high APAP levels (>150 mg/dL) may be at a reduced risk for anaphylactoid reactions (Pakravan, 2008; Waring, 2008).
Disease-related concerns: Acute APAP poisoning: Appropriate use: Acetylcysteine is indicated in patients with a serum APAP level that indicates they are at "possible" risk or greater for hepatotoxicity when plotted on the Rumack-Matthew nomogram. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained <4>24 hours after an acute ingestion or patients who present following an acute ingestion at an unknown time may be candidates for acetylcysteine therapy; consultation with a poison control center or clinical toxicologist is highly recommended. Repeated supratherapeutic ingestion (RSTI) of APAP: Appropriate use: The Rumack-Matthew nomogram is not designed to be used following RSTIs. In general, an accurate past medical history, including a comprehensive APAP ingestion history, in conjunction with AST concentrations and serum APAP levels, may give the clinician insight as to the patient's risk of APAP toxicity. Some experts recommend that acetylcysteine be administered to any patient with "higher than expected" serum APAP levels or serum APAP level >10 mcg/mL, even in the absence of hepatic injury; others recommend treatment for patients with laboratory evidence and/or signs and symptoms of hepatotoxicity (Hendrickson, 2006; Jones, 2000). Consultation with a poison control center or a clinical toxicologist is highly recommended.
Dosage form specific issues: Inhalation: Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow. If bronchospasm occurs, administer a bronchodilator; discontinue acetylcysteine if bronchospasm progresses.
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Based on limited reports using acetylcysteine to treat acetaminophen poisoning in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective levels in the fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Solution (Acetylcysteine)
10% (30): $17.99
10% (30): $25.99
20% (4): $7.99
20% (10): $22.99
Solution (Mucomyst-10)
10% (30): $18.99
MONITORING PARAMETERS — Acetaminophen poisoning: Monitor patient for the development of anaphylaxis or anaphylactoid reactions; monitor serum APAP levels, AST, ALT, bilirubin, PT, INR, serum creatinine, BUN, serum glucose, hemoglobin, hematocrit, and electrolytes. Assess patient for nausea, vomiting, and skin rash following oral administration. Reassess LFTs for possible hepatotoxicity every 4-6 hours.
Acute ingestion: Obtain the first APAP level 4 hours postingestion (or as soon as possible thereafter); plot on the Rumack-Matthew nomogram. In patients who have ingested an extended release formulation of APAP or have coingested an agent known to delay gastric emptying, obtain a repeat serum APAP measurement 4-6 hours following the first measurement if the original level (taken at 4-8 hours postingestion) when plotted on the Rumack-Matthew nomogram indicated that treatment was not necessary.
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
INTERNATIONAL BRAND NAMES — ACC (AR, HU, LU, MX, PL, ZA); ACC 200 (EE, HN); Acemuk (AR); Acet (TW); Acetain (KP); Acetin (MY); Acetylcystein NM Pharma (SE); Acetylcystein Tika (SE); Acypront (HK, PL); Alistine Forte (TH); Bromuc (BR); Broncoflem (PH); Cystaline (TH); Drenaflen (EC); Ecomucyl (CH); Eloamin (CZ); Exomuc (FR, HK, LU); Fabrol (AT, GR); Flemex AC (TH); Fluimicil (CH, DE); Fluimiquil (LU); Fluimucil (AR, BG, BR, CL, CO, HK, HU, ID, IT, MA, NL, PE, PL, TH, TW); Fluimucil A (MY, PK); Fluimukan (HR); Flumil (ES); Flutafin (TW); Hidonac (ID, MY, PH, TH, TW); L-Cimexyl (SG); Libramucil (EC); Lubrisec (AR); Lysomucil (LU); Lysox (LU); Madame Pearl's Mucolytic (HK); Menaxol (CR, DO, GT, HN, NI, PA, SV); Mucofillin (JP); Mucolair (LU); Mucolator (LU, MY); Mucolitico (CN); Mucomiste (PT); Mucomyst (AT, AU, BE, DK, FI, FR, KP, LU, NO, SE); Mucomystendo (FR); Mucoserin (KP); Mucosof (CL); Mucosten (KP); Mucosys (IN); Mucoza (TH); Mukolit (ID); Muteran (KP); Muxatil (PY); NAC-ratiopharm (LU); Parvolex (GB, IE, NZ, PH); Pectocil (ID); Pectomucil (LU); Reolin (IL); Rumicil (LU); Siran (ID); Siran 200 (IL); Solmucol (HU, LU); Spatam (SG); Sputopur (HU); Stecin (KP); Stenac (TH); Syntemucol (PL); Touxium Mucolyticum (LU); Tussicom (PL); Viskoferm (SE)
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity.
In patients with APAP toxicity, acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of APAP.
The presumed mechanism in preventing contrast-induced nephropathy is its ability to scavenge oxygen-derived free radicals and improve endothelium-dependent vasodilation.
PHARMACODYNAMICS / KINETICS
Onset of action: Inhalation: 5-10 minutes
Duration: Inhalation: >1 hour
Distribution: 0.47 L/kg
Protein binding: 83%
Half-life elimination:
Reduced acetylcysteine: 2 hours
Total acetylcysteine: Adults: 5.6 hours; Newborns: 11 hours
Time to peak, plasma: Oral: 1-2 hours
Excretion: Urine
PATIENT INFORMATION — Clear airway by coughing deeply before using aerosol.
PHARMACOLOGIC CATEGORY
Antidote
Mucolytic Agent
DOSING: ADULTS
Acetaminophen poisoning: Only the 72-hour oral and 21-hour I.V. regimens are FDA-approved. Ideally, in patients with an acute APAP ingestion, treatment should begin within 8 hours of ingestion. In patients who present following RSTI and treatment is deemed appropriate, acetylcysteine should be initiated immediately.
Oral:Note: Consultation with a poison control center or clinical toxicologist is highly recommended when considering the discontinuation of oral acetylcysteine prior to the conclusion of a full 18-dose course of therapy.
72-hour regimen: Consists of 18 doses; total dose delivered: 1330 mg/kg
Loading dose: 140 mg/kg
Maintenance dose: 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration
I.V. (Acetadote®):
21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg
Loading dose: 150 mg/kg infused over 60 minutes
Second dose: 50 mg/kg infused over 4 hours
Third dose: 100 mg/kg infused over 16 hours
Note: The fluid volume should be reduced in patients weighing <40 kg according to the following table:
Acetadote® Dosing / Fluid Volume Guidelines for Patients <40 kg
Body weight 30 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 22.5 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 7.5 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 15 mL in D5W 500 mL
Body weight 25 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 18.75 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 6.25 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 12.5 mL in D5W 500 mL
Body weight 20 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 15 mL in D5W 60 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 5 mL in D5W 140 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 10 mL in D5W 280 mL
Body weight 15 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 11.25 mL in D5W 45 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 3.75 mL in D5W 105 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 7.5 mL in D5W 210 mL
Body weight 10 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 7.5 mL in D5W 30 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 2.5 mL in D5W 70 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 5 mL in D5W 140 mL
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to dose.
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours
Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment
Direct instillation:
Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours
Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter
Diagnostic bronchogram: Nebulization or intratracheal: 1-2 mL of 20% solution or 2-4 mL of 10% solution administered 2-3 times prior to procedure
Prevention of contrast-induced nephropathy (CIN) (unlabeled use): Oral: 600-1200 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules (some centers use solution, diluted in cola beverage or juice)
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use):I.V.: 1200 mg over 5-10 minutes prior to cardiac catheterization, followed by 1200 mg orally twice daily for 48 hours
DOSING: PEDIATRIC
(For additional information see "Acetylcysteine: Pediatric drug information")
Acetaminophen poisoning: Refer to adult dosing.
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted.
Infants: 1-2 mL of 20% solution or 2-4 mL 10% solution until nebulized given 3-4 times/day
Children: Refer to adult dosing.
Inhalation, nebulization (tent, croupette): Children: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL; contains disodium edetate]
Solution, inhalation/oral: 10% (4 mL, 10 mL, 30 mL) [100 mg/mL]; 20% (4 mL, 10 mL, 30 mL) [200 mg/mL]
DOSAGE FORMS: CONCISE
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL]
Solution, inhalation/oral: 10% [100 mg/mL]; 20% [200 mg/mL]
GENERIC EQUIVALENT AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION
Inhalation: Acetylcysteine is incompatible with tetracyclines, erythromycin, amphotericin B, iodized oil, chymotrypsin, trypsin, and hydrogen peroxide. Administer separately. Intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime.
Oral: Treatment of APAP poisoning, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).
I.V. (Acetadote®):
Acetaminophen poisoning:
Loading dose: Dilute in D5W 200 mL; administer over 60 minutes.
Second dose: Dilute in D5W 500 mL; administer over 4 hours.
Third dose: Dilute in D5W 1000 mL; administer over 16 hours.
Note: To avoid fluid overload in patients <40 kg and those requiring fluid restriction, decrease volume of D5W proportionally (see table in dosing section). Discard unused portion.
If the commercial I.V. form is unavailable, the solution for inhalation has been used; each dose should be infused through a 0.2 micron Millipore filter (in-line) over 60 minutes (Yip, 1998); intravenous administration of the solution for inhalation is not USP 797-compliant.
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use): Administer 1200 mg I.V. push over 5-10 minutes prior to contrast administration.
COMPATIBILITY
Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, tetracycline, oxytetracycline, erythromycin.
Intravenous: Compatible with D5W, 1/2NS, SWFI. Incompatible with rubber, metals (particularly iron, copper, and nickel), cefepime, and ceftazidime.
USE — Antidote for acute acetaminophen (APAP) poisoning; repeated supratherapeutic ingestion (RSTI) of APAP; adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies
USE - UNLABELED / INVESTIGATIONAL — Prevention of contrast-induced renal dysfunction (oral, I.V.); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)
ADVERSE REACTIONS SIGNIFICANT
Inhalation: Frequency not defined.
Central nervous system: Drowsiness, chills, fever
Gastrointestinal: Vomiting, nausea, stomatitis
Local: Irritation, stickiness on face following nebulization
Respiratory: Bronchospasm, rhinorrhea, hemoptysis
Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration
Intravenous:
>10%: Miscellaneous: Anaphylactoid reaction (8% to 18%; shorter infusion periods [eg, <60 minutes] associated with increased incidence)
1% to 10%:
Cardiovascular: Flushing (1% to 8%), tachycardia (1% to 4%), edema (1% to 2%)
Dermatologic: Urticaria (6% to 8%), rash (2% to 4%), pruritus (1% to 4%)
Gastrointestinal: Vomiting (2% to 10%), nausea (1% to 6%)
Respiratory: Pharyngitis (≤ 1%), rhinorrhea (≤ 1%), rhonchi (≤ 1%), throat tightness (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylaxis, bronchospasm, chest tightness, cough, dyspnea, hypotension, respiratory distress, stridor, wheezing
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid reactions: Acute flushing and erythema have been reported; usually occurs within 30-60 minutes and may resolve spontaneously. Serious anaphylactoid reactions have also been reported and are more commonly associated with I.V. administration. When used for APAP poisoning, the incidence is reduced when the initial loading dose is administered over 60 minutes. Acetylcysteine infusion may be interrupted until treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactoid reactions should be immediately available. Use caution in patients with asthma or history of bronchospasm as these patients may be at increased risk. Conversely, patients with high APAP levels (>150 mg/dL) may be at a reduced risk for anaphylactoid reactions (Pakravan, 2008; Waring, 2008).
Disease-related concerns: Acute APAP poisoning: Appropriate use: Acetylcysteine is indicated in patients with a serum APAP level that indicates they are at "possible" risk or greater for hepatotoxicity when plotted on the Rumack-Matthew nomogram. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained <4>24 hours after an acute ingestion or patients who present following an acute ingestion at an unknown time may be candidates for acetylcysteine therapy; consultation with a poison control center or clinical toxicologist is highly recommended. Repeated supratherapeutic ingestion (RSTI) of APAP: Appropriate use: The Rumack-Matthew nomogram is not designed to be used following RSTIs. In general, an accurate past medical history, including a comprehensive APAP ingestion history, in conjunction with AST concentrations and serum APAP levels, may give the clinician insight as to the patient's risk of APAP toxicity. Some experts recommend that acetylcysteine be administered to any patient with "higher than expected" serum APAP levels or serum APAP level >10 mcg/mL, even in the absence of hepatic injury; others recommend treatment for patients with laboratory evidence and/or signs and symptoms of hepatotoxicity (Hendrickson, 2006; Jones, 2000). Consultation with a poison control center or a clinical toxicologist is highly recommended.
Dosage form specific issues: Inhalation: Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow. If bronchospasm occurs, administer a bronchodilator; discontinue acetylcysteine if bronchospasm progresses.
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Based on limited reports using acetylcysteine to treat acetaminophen poisoning in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective levels in the fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Solution (Acetylcysteine)
10% (30): $17.99
10% (30): $25.99
20% (4): $7.99
20% (10): $22.99
Solution (Mucomyst-10)
10% (30): $18.99
MONITORING PARAMETERS — Acetaminophen poisoning: Monitor patient for the development of anaphylaxis or anaphylactoid reactions; monitor serum APAP levels, AST, ALT, bilirubin, PT, INR, serum creatinine, BUN, serum glucose, hemoglobin, hematocrit, and electrolytes. Assess patient for nausea, vomiting, and skin rash following oral administration. Reassess LFTs for possible hepatotoxicity every 4-6 hours.
Acute ingestion: Obtain the first APAP level 4 hours postingestion (or as soon as possible thereafter); plot on the Rumack-Matthew nomogram. In patients who have ingested an extended release formulation of APAP or have coingested an agent known to delay gastric emptying, obtain a repeat serum APAP measurement 4-6 hours following the first measurement if the original level (taken at 4-8 hours postingestion) when plotted on the Rumack-Matthew nomogram indicated that treatment was not necessary.
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
INTERNATIONAL BRAND NAMES — ACC (AR, HU, LU, MX, PL, ZA); ACC 200 (EE, HN); Acemuk (AR); Acet (TW); Acetain (KP); Acetin (MY); Acetylcystein NM Pharma (SE); Acetylcystein Tika (SE); Acypront (HK, PL); Alistine Forte (TH); Bromuc (BR); Broncoflem (PH); Cystaline (TH); Drenaflen (EC); Ecomucyl (CH); Eloamin (CZ); Exomuc (FR, HK, LU); Fabrol (AT, GR); Flemex AC (TH); Fluimicil (CH, DE); Fluimiquil (LU); Fluimucil (AR, BG, BR, CL, CO, HK, HU, ID, IT, MA, NL, PE, PL, TH, TW); Fluimucil A (MY, PK); Fluimukan (HR); Flumil (ES); Flutafin (TW); Hidonac (ID, MY, PH, TH, TW); L-Cimexyl (SG); Libramucil (EC); Lubrisec (AR); Lysomucil (LU); Lysox (LU); Madame Pearl's Mucolytic (HK); Menaxol (CR, DO, GT, HN, NI, PA, SV); Mucofillin (JP); Mucolair (LU); Mucolator (LU, MY); Mucolitico (CN); Mucomiste (PT); Mucomyst (AT, AU, BE, DK, FI, FR, KP, LU, NO, SE); Mucomystendo (FR); Mucoserin (KP); Mucosof (CL); Mucosten (KP); Mucosys (IN); Mucoza (TH); Mukolit (ID); Muteran (KP); Muxatil (PY); NAC-ratiopharm (LU); Parvolex (GB, IE, NZ, PH); Pectocil (ID); Pectomucil (LU); Reolin (IL); Rumicil (LU); Siran (ID); Siran 200 (IL); Solmucol (HU, LU); Spatam (SG); Sputopur (HU); Stecin (KP); Stenac (TH); Syntemucol (PL); Touxium Mucolyticum (LU); Tussicom (PL); Viskoferm (SE)
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity.
In patients with APAP toxicity, acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of APAP.
The presumed mechanism in preventing contrast-induced nephropathy is its ability to scavenge oxygen-derived free radicals and improve endothelium-dependent vasodilation.
PHARMACODYNAMICS / KINETICS
Onset of action: Inhalation: 5-10 minutes
Duration: Inhalation: >1 hour
Distribution: 0.47 L/kg
Protein binding: 83%
Half-life elimination:
Reduced acetylcysteine: 2 hours
Total acetylcysteine: Adults: 5.6 hours; Newborns: 11 hours
Time to peak, plasma: Oral: 1-2 hours
Excretion: Urine
PATIENT INFORMATION — Clear airway by coughing deeply before using aerosol.
Acetylcysteine
U.S. BRAND NAMES — Acetadote®
PHARMACOLOGIC CATEGORY
Antidote
Mucolytic Agent
DOSING: ADULTS
Acetaminophen poisoning: Only the 72-hour oral and 21-hour I.V. regimens are FDA-approved. Ideally, in patients with an acute APAP ingestion, treatment should begin within 8 hours of ingestion. In patients who present following RSTI and treatment is deemed appropriate, acetylcysteine should be initiated immediately.
Oral:Note: Consultation with a poison control center or clinical toxicologist is highly recommended when considering the discontinuation of oral acetylcysteine prior to the conclusion of a full 18-dose course of therapy.
72-hour regimen: Consists of 18 doses; total dose delivered: 1330 mg/kg
Loading dose: 140 mg/kg
Maintenance dose: 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration
I.V. (Acetadote®):
21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg
Loading dose: 150 mg/kg infused over 60 minutes
Second dose: 50 mg/kg infused over 4 hours
Third dose: 100 mg/kg infused over 16 hours
Note: The fluid volume should be reduced in patients weighing <40 kg according to the following table:
Acetadote® Dosing / Fluid Volume Guidelines for Patients <40 kg
Body weight 30 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 22.5 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 7.5 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 15 mL in D5W 500 mL
Body weight 25 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 18.75 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 6.25 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 12.5 mL in D5W 500 mL
Body weight 20 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 15 mL in D5W 60 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 5 mL in D5W 140 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 10 mL in D5W 280 mL
Body weight 15 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 11.25 mL in D5W 45 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 3.75 mL in D5W 105 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 7.5 mL in D5W 210 mL
Body weight 10 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 7.5 mL in D5W 30 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 2.5 mL in D5W 70 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 5 mL in D5W 140 mL
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to dose.
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours
Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment
Direct instillation:
Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours
Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter
Diagnostic bronchogram: Nebulization or intratracheal: 1-2 mL of 20% solution or 2-4 mL of 10% solution administered 2-3 times prior to procedure
Prevention of contrast-induced nephropathy (CIN) (unlabeled use): Oral: 600-1200 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules (some centers use solution, diluted in cola beverage or juice)
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use):I.V.: 1200 mg over 5-10 minutes prior to cardiac catheterization, followed by 1200 mg orally twice daily for 48 hours
DOSING: PEDIATRIC
(For additional information see "Acetylcysteine: Pediatric drug information")
Acetaminophen poisoning: Refer to adult dosing.
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted.
Infants: 1-2 mL of 20% solution or 2-4 mL 10% solution until nebulized given 3-4 times/day
Children: Refer to adult dosing.
Inhalation, nebulization (tent, croupette): Children: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL; contains disodium edetate]
Solution, inhalation/oral: 10% (4 mL, 10 mL, 30 mL) [100 mg/mL]; 20% (4 mL, 10 mL, 30 mL) [200 mg/mL]
DOSAGE FORMS: CONCISE
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL]
Solution, inhalation/oral: 10% [100 mg/mL]; 20% [200 mg/mL]
GENERIC EQUIVALENT AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION
Inhalation: Acetylcysteine is incompatible with tetracyclines, erythromycin, amphotericin B, iodized oil, chymotrypsin, trypsin, and hydrogen peroxide. Administer separately. Intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime.
Oral: Treatment of APAP poisoning, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).
I.V. (Acetadote®):
Acetaminophen poisoning:
Loading dose: Dilute in D5W 200 mL; administer over 60 minutes.
Second dose: Dilute in D5W 500 mL; administer over 4 hours.
Third dose: Dilute in D5W 1000 mL; administer over 16 hours.
Note: To avoid fluid overload in patients <40 kg and those requiring fluid restriction, decrease volume of D5W proportionally (see table in dosing section). Discard unused portion.
If the commercial I.V. form is unavailable, the solution for inhalation has been used; each dose should be infused through a 0.2 micron Millipore filter (in-line) over 60 minutes (Yip, 1998); intravenous administration of the solution for inhalation is not USP 797-compliant.
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use): Administer 1200 mg I.V. push over 5-10 minutes prior to contrast administration.
COMPATIBILITY
Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, tetracycline, oxytetracycline, erythromycin.
Intravenous: Compatible with D5W, 1/2NS, SWFI. Incompatible with rubber, metals (particularly iron, copper, and nickel), cefepime, and ceftazidime.
USE — Antidote for acute acetaminophen (APAP) poisoning; repeated supratherapeutic ingestion (RSTI) of APAP; adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies
USE - UNLABELED / INVESTIGATIONAL — Prevention of contrast-induced renal dysfunction (oral, I.V.); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)
ADVERSE REACTIONS SIGNIFICANT
Inhalation: Frequency not defined.
Central nervous system: Drowsiness, chills, fever
Gastrointestinal: Vomiting, nausea, stomatitis
Local: Irritation, stickiness on face following nebulization
Respiratory: Bronchospasm, rhinorrhea, hemoptysis
Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration
Intravenous:
>10%: Miscellaneous: Anaphylactoid reaction (8% to 18%; shorter infusion periods [eg, <60 minutes] associated with increased incidence)
1% to 10%:
Cardiovascular: Flushing (1% to 8%), tachycardia (1% to 4%), edema (1% to 2%)
Dermatologic: Urticaria (6% to 8%), rash (2% to 4%), pruritus (1% to 4%)
Gastrointestinal: Vomiting (2% to 10%), nausea (1% to 6%)
Respiratory: Pharyngitis (≤ 1%), rhinorrhea (≤ 1%), rhonchi (≤ 1%), throat tightness (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylaxis, bronchospasm, chest tightness, cough, dyspnea, hypotension, respiratory distress, stridor, wheezing
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid reactions: Acute flushing and erythema have been reported; usually occurs within 30-60 minutes and may resolve spontaneously. Serious anaphylactoid reactions have also been reported and are more commonly associated with I.V. administration. When used for APAP poisoning, the incidence is reduced when the initial loading dose is administered over 60 minutes. Acetylcysteine infusion may be interrupted until treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactoid reactions should be immediately available. Use caution in patients with asthma or history of bronchospasm as these patients may be at increased risk. Conversely, patients with high APAP levels (>150 mg/dL) may be at a reduced risk for anaphylactoid reactions (Pakravan, 2008; Waring, 2008).
Disease-related concerns: Acute APAP poisoning: Appropriate use: Acetylcysteine is indicated in patients with a serum APAP level that indicates they are at "possible" risk or greater for hepatotoxicity when plotted on the Rumack-Matthew nomogram. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained <4>24 hours after an acute ingestion or patients who present following an acute ingestion at an unknown time may be candidates for acetylcysteine therapy; consultation with a poison control center or clinical toxicologist is highly recommended. Repeated supratherapeutic ingestion (RSTI) of APAP: Appropriate use: The Rumack-Matthew nomogram is not designed to be used following RSTIs. In general, an accurate past medical history, including a comprehensive APAP ingestion history, in conjunction with AST concentrations and serum APAP levels, may give the clinician insight as to the patient's risk of APAP toxicity. Some experts recommend that acetylcysteine be administered to any patient with "higher than expected" serum APAP levels or serum APAP level >10 mcg/mL, even in the absence of hepatic injury; others recommend treatment for patients with laboratory evidence and/or signs and symptoms of hepatotoxicity (Hendrickson, 2006; Jones, 2000). Consultation with a poison control center or a clinical toxicologist is highly recommended.
Dosage form specific issues: Inhalation: Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow. If bronchospasm occurs, administer a bronchodilator; discontinue acetylcysteine if bronchospasm progresses.
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Based on limited reports using acetylcysteine to treat acetaminophen poisoning in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective levels in the fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Solution (Acetylcysteine)
10% (30): $17.99
10% (30): $25.99
20% (4): $7.99
20% (10): $22.99
Solution (Mucomyst-10)
10% (30): $18.99
MONITORING PARAMETERS — Acetaminophen poisoning: Monitor patient for the development of anaphylaxis or anaphylactoid reactions; monitor serum APAP levels, AST, ALT, bilirubin, PT, INR, serum creatinine, BUN, serum glucose, hemoglobin, hematocrit, and electrolytes. Assess patient for nausea, vomiting, and skin rash following oral administration. Reassess LFTs for possible hepatotoxicity every 4-6 hours.
Acute ingestion: Obtain the first APAP level 4 hours postingestion (or as soon as possible thereafter); plot on the Rumack-Matthew nomogram. In patients who have ingested an extended release formulation of APAP or have coingested an agent known to delay gastric emptying, obtain a repeat serum APAP measurement 4-6 hours following the first measurement if the original level (taken at 4-8 hours postingestion) when plotted on the Rumack-Matthew nomogram indicated that treatment was not necessary.
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
INTERNATIONAL BRAND NAMES — ACC (AR, HU, LU, MX, PL, ZA); ACC 200 (EE, HN); Acemuk (AR); Acet (TW); Acetain (KP); Acetin (MY); Acetylcystein NM Pharma (SE); Acetylcystein Tika (SE); Acypront (HK, PL); Alistine Forte (TH); Bromuc (BR); Broncoflem (PH); Cystaline (TH); Drenaflen (EC); Ecomucyl (CH); Eloamin (CZ); Exomuc (FR, HK, LU); Fabrol (AT, GR); Flemex AC (TH); Fluimicil (CH, DE); Fluimiquil (LU); Fluimucil (AR, BG, BR, CL, CO, HK, HU, ID, IT, MA, NL, PE, PL, TH, TW); Fluimucil A (MY, PK); Fluimukan (HR); Flumil (ES); Flutafin (TW); Hidonac (ID, MY, PH, TH, TW); L-Cimexyl (SG); Libramucil (EC); Lubrisec (AR); Lysomucil (LU); Lysox (LU); Madame Pearl's Mucolytic (HK); Menaxol (CR, DO, GT, HN, NI, PA, SV); Mucofillin (JP); Mucolair (LU); Mucolator (LU, MY); Mucolitico (CN); Mucomiste (PT); Mucomyst (AT, AU, BE, DK, FI, FR, KP, LU, NO, SE); Mucomystendo (FR); Mucoserin (KP); Mucosof (CL); Mucosten (KP); Mucosys (IN); Mucoza (TH); Mukolit (ID); Muteran (KP); Muxatil (PY); NAC-ratiopharm (LU); Parvolex (GB, IE, NZ, PH); Pectocil (ID); Pectomucil (LU); Reolin (IL); Rumicil (LU); Siran (ID); Siran 200 (IL); Solmucol (HU, LU); Spatam (SG); Sputopur (HU); Stecin (KP); Stenac (TH); Syntemucol (PL); Touxium Mucolyticum (LU); Tussicom (PL); Viskoferm (SE)
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity.
In patients with APAP toxicity, acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of APAP.
The presumed mechanism in preventing contrast-induced nephropathy is its ability to scavenge oxygen-derived free radicals and improve endothelium-dependent vasodilation.
PHARMACODYNAMICS / KINETICS
Onset of action: Inhalation: 5-10 minutes
Duration: Inhalation: >1 hour
Distribution: 0.47 L/kg
Protein binding: 83%
Half-life elimination:
Reduced acetylcysteine: 2 hours
Total acetylcysteine: Adults: 5.6 hours; Newborns: 11 hours
Time to peak, plasma: Oral: 1-2 hours
Excretion: Urine
PATIENT INFORMATION — Clear airway by coughing deeply before using aerosol.
PHARMACOLOGIC CATEGORY
Antidote
Mucolytic Agent
DOSING: ADULTS
Acetaminophen poisoning: Only the 72-hour oral and 21-hour I.V. regimens are FDA-approved. Ideally, in patients with an acute APAP ingestion, treatment should begin within 8 hours of ingestion. In patients who present following RSTI and treatment is deemed appropriate, acetylcysteine should be initiated immediately.
Oral:Note: Consultation with a poison control center or clinical toxicologist is highly recommended when considering the discontinuation of oral acetylcysteine prior to the conclusion of a full 18-dose course of therapy.
72-hour regimen: Consists of 18 doses; total dose delivered: 1330 mg/kg
Loading dose: 140 mg/kg
Maintenance dose: 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration
I.V. (Acetadote®):
21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg
Loading dose: 150 mg/kg infused over 60 minutes
Second dose: 50 mg/kg infused over 4 hours
Third dose: 100 mg/kg infused over 16 hours
Note: The fluid volume should be reduced in patients weighing <40 kg according to the following table:
Acetadote® Dosing / Fluid Volume Guidelines for Patients <40 kg
Body weight 30 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 22.5 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 7.5 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 15 mL in D5W 500 mL
Body weight 25 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 18.75 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 6.25 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 12.5 mL in D5W 500 mL
Body weight 20 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 15 mL in D5W 60 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 5 mL in D5W 140 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 10 mL in D5W 280 mL
Body weight 15 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 11.25 mL in D5W 45 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 3.75 mL in D5W 105 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 7.5 mL in D5W 210 mL
Body weight 10 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 7.5 mL in D5W 30 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 2.5 mL in D5W 70 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 5 mL in D5W 140 mL
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to dose.
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours
Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment
Direct instillation:
Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours
Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter
Diagnostic bronchogram: Nebulization or intratracheal: 1-2 mL of 20% solution or 2-4 mL of 10% solution administered 2-3 times prior to procedure
Prevention of contrast-induced nephropathy (CIN) (unlabeled use): Oral: 600-1200 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules (some centers use solution, diluted in cola beverage or juice)
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use):I.V.: 1200 mg over 5-10 minutes prior to cardiac catheterization, followed by 1200 mg orally twice daily for 48 hours
DOSING: PEDIATRIC
(For additional information see "Acetylcysteine: Pediatric drug information")
Acetaminophen poisoning: Refer to adult dosing.
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted.
Infants: 1-2 mL of 20% solution or 2-4 mL 10% solution until nebulized given 3-4 times/day
Children: Refer to adult dosing.
Inhalation, nebulization (tent, croupette): Children: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL; contains disodium edetate]
Solution, inhalation/oral: 10% (4 mL, 10 mL, 30 mL) [100 mg/mL]; 20% (4 mL, 10 mL, 30 mL) [200 mg/mL]
DOSAGE FORMS: CONCISE
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL]
Solution, inhalation/oral: 10% [100 mg/mL]; 20% [200 mg/mL]
GENERIC EQUIVALENT AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION
Inhalation: Acetylcysteine is incompatible with tetracyclines, erythromycin, amphotericin B, iodized oil, chymotrypsin, trypsin, and hydrogen peroxide. Administer separately. Intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime.
Oral: Treatment of APAP poisoning, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).
I.V. (Acetadote®):
Acetaminophen poisoning:
Loading dose: Dilute in D5W 200 mL; administer over 60 minutes.
Second dose: Dilute in D5W 500 mL; administer over 4 hours.
Third dose: Dilute in D5W 1000 mL; administer over 16 hours.
Note: To avoid fluid overload in patients <40 kg and those requiring fluid restriction, decrease volume of D5W proportionally (see table in dosing section). Discard unused portion.
If the commercial I.V. form is unavailable, the solution for inhalation has been used; each dose should be infused through a 0.2 micron Millipore filter (in-line) over 60 minutes (Yip, 1998); intravenous administration of the solution for inhalation is not USP 797-compliant.
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use): Administer 1200 mg I.V. push over 5-10 minutes prior to contrast administration.
COMPATIBILITY
Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, tetracycline, oxytetracycline, erythromycin.
Intravenous: Compatible with D5W, 1/2NS, SWFI. Incompatible with rubber, metals (particularly iron, copper, and nickel), cefepime, and ceftazidime.
USE — Antidote for acute acetaminophen (APAP) poisoning; repeated supratherapeutic ingestion (RSTI) of APAP; adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies
USE - UNLABELED / INVESTIGATIONAL — Prevention of contrast-induced renal dysfunction (oral, I.V.); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)
ADVERSE REACTIONS SIGNIFICANT
Inhalation: Frequency not defined.
Central nervous system: Drowsiness, chills, fever
Gastrointestinal: Vomiting, nausea, stomatitis
Local: Irritation, stickiness on face following nebulization
Respiratory: Bronchospasm, rhinorrhea, hemoptysis
Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration
Intravenous:
>10%: Miscellaneous: Anaphylactoid reaction (8% to 18%; shorter infusion periods [eg, <60 minutes] associated with increased incidence)
1% to 10%:
Cardiovascular: Flushing (1% to 8%), tachycardia (1% to 4%), edema (1% to 2%)
Dermatologic: Urticaria (6% to 8%), rash (2% to 4%), pruritus (1% to 4%)
Gastrointestinal: Vomiting (2% to 10%), nausea (1% to 6%)
Respiratory: Pharyngitis (≤ 1%), rhinorrhea (≤ 1%), rhonchi (≤ 1%), throat tightness (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylaxis, bronchospasm, chest tightness, cough, dyspnea, hypotension, respiratory distress, stridor, wheezing
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid reactions: Acute flushing and erythema have been reported; usually occurs within 30-60 minutes and may resolve spontaneously. Serious anaphylactoid reactions have also been reported and are more commonly associated with I.V. administration. When used for APAP poisoning, the incidence is reduced when the initial loading dose is administered over 60 minutes. Acetylcysteine infusion may be interrupted until treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactoid reactions should be immediately available. Use caution in patients with asthma or history of bronchospasm as these patients may be at increased risk. Conversely, patients with high APAP levels (>150 mg/dL) may be at a reduced risk for anaphylactoid reactions (Pakravan, 2008; Waring, 2008).
Disease-related concerns: Acute APAP poisoning: Appropriate use: Acetylcysteine is indicated in patients with a serum APAP level that indicates they are at "possible" risk or greater for hepatotoxicity when plotted on the Rumack-Matthew nomogram. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained <4>24 hours after an acute ingestion or patients who present following an acute ingestion at an unknown time may be candidates for acetylcysteine therapy; consultation with a poison control center or clinical toxicologist is highly recommended. Repeated supratherapeutic ingestion (RSTI) of APAP: Appropriate use: The Rumack-Matthew nomogram is not designed to be used following RSTIs. In general, an accurate past medical history, including a comprehensive APAP ingestion history, in conjunction with AST concentrations and serum APAP levels, may give the clinician insight as to the patient's risk of APAP toxicity. Some experts recommend that acetylcysteine be administered to any patient with "higher than expected" serum APAP levels or serum APAP level >10 mcg/mL, even in the absence of hepatic injury; others recommend treatment for patients with laboratory evidence and/or signs and symptoms of hepatotoxicity (Hendrickson, 2006; Jones, 2000). Consultation with a poison control center or a clinical toxicologist is highly recommended.
Dosage form specific issues: Inhalation: Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow. If bronchospasm occurs, administer a bronchodilator; discontinue acetylcysteine if bronchospasm progresses.
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Based on limited reports using acetylcysteine to treat acetaminophen poisoning in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective levels in the fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Solution (Acetylcysteine)
10% (30): $17.99
10% (30): $25.99
20% (4): $7.99
20% (10): $22.99
Solution (Mucomyst-10)
10% (30): $18.99
MONITORING PARAMETERS — Acetaminophen poisoning: Monitor patient for the development of anaphylaxis or anaphylactoid reactions; monitor serum APAP levels, AST, ALT, bilirubin, PT, INR, serum creatinine, BUN, serum glucose, hemoglobin, hematocrit, and electrolytes. Assess patient for nausea, vomiting, and skin rash following oral administration. Reassess LFTs for possible hepatotoxicity every 4-6 hours.
Acute ingestion: Obtain the first APAP level 4 hours postingestion (or as soon as possible thereafter); plot on the Rumack-Matthew nomogram. In patients who have ingested an extended release formulation of APAP or have coingested an agent known to delay gastric emptying, obtain a repeat serum APAP measurement 4-6 hours following the first measurement if the original level (taken at 4-8 hours postingestion) when plotted on the Rumack-Matthew nomogram indicated that treatment was not necessary.
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
INTERNATIONAL BRAND NAMES — ACC (AR, HU, LU, MX, PL, ZA); ACC 200 (EE, HN); Acemuk (AR); Acet (TW); Acetain (KP); Acetin (MY); Acetylcystein NM Pharma (SE); Acetylcystein Tika (SE); Acypront (HK, PL); Alistine Forte (TH); Bromuc (BR); Broncoflem (PH); Cystaline (TH); Drenaflen (EC); Ecomucyl (CH); Eloamin (CZ); Exomuc (FR, HK, LU); Fabrol (AT, GR); Flemex AC (TH); Fluimicil (CH, DE); Fluimiquil (LU); Fluimucil (AR, BG, BR, CL, CO, HK, HU, ID, IT, MA, NL, PE, PL, TH, TW); Fluimucil A (MY, PK); Fluimukan (HR); Flumil (ES); Flutafin (TW); Hidonac (ID, MY, PH, TH, TW); L-Cimexyl (SG); Libramucil (EC); Lubrisec (AR); Lysomucil (LU); Lysox (LU); Madame Pearl's Mucolytic (HK); Menaxol (CR, DO, GT, HN, NI, PA, SV); Mucofillin (JP); Mucolair (LU); Mucolator (LU, MY); Mucolitico (CN); Mucomiste (PT); Mucomyst (AT, AU, BE, DK, FI, FR, KP, LU, NO, SE); Mucomystendo (FR); Mucoserin (KP); Mucosof (CL); Mucosten (KP); Mucosys (IN); Mucoza (TH); Mukolit (ID); Muteran (KP); Muxatil (PY); NAC-ratiopharm (LU); Parvolex (GB, IE, NZ, PH); Pectocil (ID); Pectomucil (LU); Reolin (IL); Rumicil (LU); Siran (ID); Siran 200 (IL); Solmucol (HU, LU); Spatam (SG); Sputopur (HU); Stecin (KP); Stenac (TH); Syntemucol (PL); Touxium Mucolyticum (LU); Tussicom (PL); Viskoferm (SE)
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity.
In patients with APAP toxicity, acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of APAP.
The presumed mechanism in preventing contrast-induced nephropathy is its ability to scavenge oxygen-derived free radicals and improve endothelium-dependent vasodilation.
PHARMACODYNAMICS / KINETICS
Onset of action: Inhalation: 5-10 minutes
Duration: Inhalation: >1 hour
Distribution: 0.47 L/kg
Protein binding: 83%
Half-life elimination:
Reduced acetylcysteine: 2 hours
Total acetylcysteine: Adults: 5.6 hours; Newborns: 11 hours
Time to peak, plasma: Oral: 1-2 hours
Excretion: Urine
PATIENT INFORMATION — Clear airway by coughing deeply before using aerosol.
Acetylcholine
U.S. BRAND NAMES — Miochol®-E
PHARMACOLOGIC CATEGORY
Cholinergic Agonist
Ophthalmic Agent, Miotic
DOSING: ADULTS — To produce miosis: Intraocular: 0.5-2 mL of 1% injection (5-20 mg) instilled into anterior chamber before or after securing one or more sutures
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride:
Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
DOSAGE FORMS: CONCISE
Powder for intraocular solution:
Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Open under aseptic conditions only. Attach filter before irrigating eye.
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy, and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Bradycardia, flushing, hypotension
Central nervous system: Headache
Ocular: Clouding, corneal edema, decompensation
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component of the formulation; acute iritis and acute inflammatory disease of the anterior chamber
WARNINGS / PRECAUTIONS
Disease-related concerns: Diseases affected by systemic effects: Systemic effects rarely occur but can cause problems for patients with asthma, GI spasm, acute heart failure, hyperthyroidism, Parkinson's disease, peptic ulcer disease, and or urinary tract obstruction.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Aseptic conditions: Open under aseptic conditions only. Cataract surgery: During cataract surgery, use only after lens is in place.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Acetylcholine is used primarily in the eye and there are no reports of its use in pregnancy. Because it is ionized at physiologic pH, transplacental passage would not be expected.
CANADIAN BRAND NAMES — Miochol®-E
INTERNATIONAL BRAND NAMES — Acetilcolina Colirio (AR); Acetilcolina Cusi (ES); Miochol (FI, GR, LU, NL, NZ); Miochol-E (AU, BE, CH, CN, DE, DK, FI, GB, HK, ID, IE, IL, IT, KP, NL, NO, SE, ZA); Miochole (FR); Miovisin (IT); OQ-Miot (CO)
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation spasm
PHARMACODYNAMICS / KINETICS
Onset of action: Rapid
Duration: ~10 minutes
PATIENT INFORMATION — Do not touch dropper to eye. May sting on instillation. Use caution while driving at night or performing hazardous tasks.
PHARMACOLOGIC CATEGORY
Cholinergic Agonist
Ophthalmic Agent, Miotic
DOSING: ADULTS — To produce miosis: Intraocular: 0.5-2 mL of 1% injection (5-20 mg) instilled into anterior chamber before or after securing one or more sutures
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride:
Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
DOSAGE FORMS: CONCISE
Powder for intraocular solution:
Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Open under aseptic conditions only. Attach filter before irrigating eye.
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy, and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Bradycardia, flushing, hypotension
Central nervous system: Headache
Ocular: Clouding, corneal edema, decompensation
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component of the formulation; acute iritis and acute inflammatory disease of the anterior chamber
WARNINGS / PRECAUTIONS
Disease-related concerns: Diseases affected by systemic effects: Systemic effects rarely occur but can cause problems for patients with asthma, GI spasm, acute heart failure, hyperthyroidism, Parkinson's disease, peptic ulcer disease, and or urinary tract obstruction.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Aseptic conditions: Open under aseptic conditions only. Cataract surgery: During cataract surgery, use only after lens is in place.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Acetylcholine is used primarily in the eye and there are no reports of its use in pregnancy. Because it is ionized at physiologic pH, transplacental passage would not be expected.
CANADIAN BRAND NAMES — Miochol®-E
INTERNATIONAL BRAND NAMES — Acetilcolina Colirio (AR); Acetilcolina Cusi (ES); Miochol (FI, GR, LU, NL, NZ); Miochol-E (AU, BE, CH, CN, DE, DK, FI, GB, HK, ID, IE, IL, IT, KP, NL, NO, SE, ZA); Miochole (FR); Miovisin (IT); OQ-Miot (CO)
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation spasm
PHARMACODYNAMICS / KINETICS
Onset of action: Rapid
Duration: ~10 minutes
PATIENT INFORMATION — Do not touch dropper to eye. May sting on instillation. Use caution while driving at night or performing hazardous tasks.
Acetylcholine
U.S. BRAND NAMES — Miochol®-E
PHARMACOLOGIC CATEGORY
Cholinergic Agonist
Ophthalmic Agent, Miotic
DOSING: ADULTS — To produce miosis: Intraocular: 0.5-2 mL of 1% injection (5-20 mg) instilled into anterior chamber before or after securing one or more sutures
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride:
Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
DOSAGE FORMS: CONCISE
Powder for intraocular solution:
Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Open under aseptic conditions only. Attach filter before irrigating eye.
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy, and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Bradycardia, flushing, hypotension
Central nervous system: Headache
Ocular: Clouding, corneal edema, decompensation
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component of the formulation; acute iritis and acute inflammatory disease of the anterior chamber
WARNINGS / PRECAUTIONS
Disease-related concerns: Diseases affected by systemic effects: Systemic effects rarely occur but can cause problems for patients with asthma, GI spasm, acute heart failure, hyperthyroidism, Parkinson's disease, peptic ulcer disease, and or urinary tract obstruction.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Aseptic conditions: Open under aseptic conditions only. Cataract surgery: During cataract surgery, use only after lens is in place.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Acetylcholine is used primarily in the eye and there are no reports of its use in pregnancy. Because it is ionized at physiologic pH, transplacental passage would not be expected.
CANADIAN BRAND NAMES — Miochol®-E
INTERNATIONAL BRAND NAMES — Acetilcolina Colirio (AR); Acetilcolina Cusi (ES); Miochol (FI, GR, LU, NL, NZ); Miochol-E (AU, BE, CH, CN, DE, DK, FI, GB, HK, ID, IE, IL, IT, KP, NL, NO, SE, ZA); Miochole (FR); Miovisin (IT); OQ-Miot (CO)
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation spasm
PHARMACODYNAMICS / KINETICS
Onset of action: Rapid
Duration: ~10 minutes
PATIENT INFORMATION — Do not touch dropper to eye. May sting on instillation. Use caution while driving at night or performing hazardous tasks.
PHARMACOLOGIC CATEGORY
Cholinergic Agonist
Ophthalmic Agent, Miotic
DOSING: ADULTS — To produce miosis: Intraocular: 0.5-2 mL of 1% injection (5-20 mg) instilled into anterior chamber before or after securing one or more sutures
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride:
Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
DOSAGE FORMS: CONCISE
Powder for intraocular solution:
Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Open under aseptic conditions only. Attach filter before irrigating eye.
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy, and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Bradycardia, flushing, hypotension
Central nervous system: Headache
Ocular: Clouding, corneal edema, decompensation
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component of the formulation; acute iritis and acute inflammatory disease of the anterior chamber
WARNINGS / PRECAUTIONS
Disease-related concerns: Diseases affected by systemic effects: Systemic effects rarely occur but can cause problems for patients with asthma, GI spasm, acute heart failure, hyperthyroidism, Parkinson's disease, peptic ulcer disease, and or urinary tract obstruction.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Aseptic conditions: Open under aseptic conditions only. Cataract surgery: During cataract surgery, use only after lens is in place.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Acetylcholine is used primarily in the eye and there are no reports of its use in pregnancy. Because it is ionized at physiologic pH, transplacental passage would not be expected.
CANADIAN BRAND NAMES — Miochol®-E
INTERNATIONAL BRAND NAMES — Acetilcolina Colirio (AR); Acetilcolina Cusi (ES); Miochol (FI, GR, LU, NL, NZ); Miochol-E (AU, BE, CH, CN, DE, DK, FI, GB, HK, ID, IE, IL, IT, KP, NL, NO, SE, ZA); Miochole (FR); Miovisin (IT); OQ-Miot (CO)
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation spasm
PHARMACODYNAMICS / KINETICS
Onset of action: Rapid
Duration: ~10 minutes
PATIENT INFORMATION — Do not touch dropper to eye. May sting on instillation. Use caution while driving at night or performing hazardous tasks.
Acetohydroxamic acid
U.S. BRAND NAMES — Lithostat®
PHARMACOLOGIC CATEGORY
Urinary Tract Product
DOSING: ADULTS — Susceptible infections: Oral: 250 mg 3-4 times/day for a total daily dose of 10-15 mg/kg/day
DOSING: PEDIATRIC — Susceptible infections: Oral: Initial: 10 mg/kg/day
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Not recommended for use in significant renal impairment (Srcr >2.5 mg/dL).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Lithostat®: 250 mg
DOSAGE FORMS: CONCISE
Tablet:
Lithostat®: 250 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Should be administered on an empty stomach.
USE — Adjunctive therapy in chronic urea-splitting urinary infection
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Deep vein thrombosis (rare), embolism, palpitation, phlebitis
Central nervous system: Anorexia, anxiety, depression, headache, malaise, nervousness, tremor
Dermatologic: Flushing (with ethanol consumption), rash (nonpruritic, macular)
Gastrointestinal: Nausea, vomiting
Hematologic: Hemolytic anemia (15% with laboratory evidence; ~3% severe requiring discontinuation; may be accompanied by GI symptoms or systemic complaints of malaise and/or fatigue); hyperbilirubinemia
Respiratory: Pulmonary embolism (rare)
CONTRAINDICATIONS — Hypersensitivity to acetohydroxamic acid or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bone marrow suppression: May suppress bone marrow function; use with caution in patients with prior bone marrow depression. Close monitoring of hematologic function is recommended. Hemolytic anemia: Has been associated with hemolytic anemia (Coombs' negative), which may be associated with gastrointestinal distress and systemic symptoms; use with caution in patients with anemia. Monitor hematologic parameters during extended therapy. Hepatotoxicity: May cause hepatic injury; close monitoring of hepatic function is recommended.
Disease-related concerns: Psychiatric disorders: Use with caution in patients with pre-existing psychiatric disorders; may be associated with nervousness, anxiety, and/or depression.
DRUG INTERACTIONS — There are no known significant interactions.
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Avoid ethanol (may increase incidence of rash and/or flushing).
Food: May decrease absorption of acetohydroxamic acid.
PREGNANCY RISK FACTOR — X (show table)
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Should be taken on an empty stomach, 1 hour before or 2 hours after meals.
PRICING — (data from drugstore.com)
Tablets (Lithostat)
250 mg (100): $172.79
MONITORING PARAMETERS — In patients receiving therapy >2 weeks, monitor CBC with reticulocytes at 3-month intervals during the duration of treatment.
CANADIAN BRAND NAMES — Lithostat®
INTERNATIONAL BRAND NAMES — Uronefrex (BE, ES, FR, LU)
MECHANISM OF ACTION — Acetohydroxamic acid inhibits bacterial urease enzymes, decreasing the formation of ammonia in the urine by urea-splitting organisms. A reduction in urinary ammonia may increase the antibacterial activity of some antibiotic agents.
PHARMACOLOGIC CATEGORY
Urinary Tract Product
DOSING: ADULTS — Susceptible infections: Oral: 250 mg 3-4 times/day for a total daily dose of 10-15 mg/kg/day
DOSING: PEDIATRIC — Susceptible infections: Oral: Initial: 10 mg/kg/day
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Not recommended for use in significant renal impairment (Srcr >2.5 mg/dL).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Lithostat®: 250 mg
DOSAGE FORMS: CONCISE
Tablet:
Lithostat®: 250 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Should be administered on an empty stomach.
USE — Adjunctive therapy in chronic urea-splitting urinary infection
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Deep vein thrombosis (rare), embolism, palpitation, phlebitis
Central nervous system: Anorexia, anxiety, depression, headache, malaise, nervousness, tremor
Dermatologic: Flushing (with ethanol consumption), rash (nonpruritic, macular)
Gastrointestinal: Nausea, vomiting
Hematologic: Hemolytic anemia (15% with laboratory evidence; ~3% severe requiring discontinuation; may be accompanied by GI symptoms or systemic complaints of malaise and/or fatigue); hyperbilirubinemia
Respiratory: Pulmonary embolism (rare)
CONTRAINDICATIONS — Hypersensitivity to acetohydroxamic acid or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bone marrow suppression: May suppress bone marrow function; use with caution in patients with prior bone marrow depression. Close monitoring of hematologic function is recommended. Hemolytic anemia: Has been associated with hemolytic anemia (Coombs' negative), which may be associated with gastrointestinal distress and systemic symptoms; use with caution in patients with anemia. Monitor hematologic parameters during extended therapy. Hepatotoxicity: May cause hepatic injury; close monitoring of hepatic function is recommended.
Disease-related concerns: Psychiatric disorders: Use with caution in patients with pre-existing psychiatric disorders; may be associated with nervousness, anxiety, and/or depression.
DRUG INTERACTIONS — There are no known significant interactions.
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Avoid ethanol (may increase incidence of rash and/or flushing).
Food: May decrease absorption of acetohydroxamic acid.
PREGNANCY RISK FACTOR — X (show table)
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Should be taken on an empty stomach, 1 hour before or 2 hours after meals.
PRICING — (data from drugstore.com)
Tablets (Lithostat)
250 mg (100): $172.79
MONITORING PARAMETERS — In patients receiving therapy >2 weeks, monitor CBC with reticulocytes at 3-month intervals during the duration of treatment.
CANADIAN BRAND NAMES — Lithostat®
INTERNATIONAL BRAND NAMES — Uronefrex (BE, ES, FR, LU)
MECHANISM OF ACTION — Acetohydroxamic acid inhibits bacterial urease enzymes, decreasing the formation of ammonia in the urine by urea-splitting organisms. A reduction in urinary ammonia may increase the antibacterial activity of some antibiotic agents.
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