U.S. BRAND NAMES — Norvasc®
PHARMACOLOGIC CATEGORY
Calcium Channel Blocker
DOSING: ADULTS
Hypertension: Oral: Initial dose: 5 mg once daily; maximum dose: 10 mg once daily. In general, titrate in 2.5 mg increments over 7-14 days. Usual dosage range (JNC 7): 2.5-10 mg once daily.
Angina: Oral: Usual dose: 5-10 mg; lower dose suggested in elderly or hepatic impairment; most patients require 10 mg for adequate effect.
DOSING: PEDIATRIC — Hypertension: Oral: Children 6-17 years: 2.5-5 mg once daily
(For additional information see "Amlodipine: Pediatric drug information")
DOSING: ELDERLY — Dosing should start at the lower end of dosing range due to possible increased incidence of hepatic, renal, or cardiac impairment. Elderly patients also show decreased clearance of amlodipine.
Hypertension: Oral: 2.5 mg once daily
Angina: Oral: 5 mg once daily
DOSING: HEPATIC IMPAIRMENT
Hypertension: Administer 2.5 mg once daily
Angina: Administer 5 mg once daily
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Norvasc®: 2.5 mg, 5 mg, 10 mg
DOSAGE FORMS: CONCISE
Tablet:
Norvasc®: 2.5 mg, 5 mg, 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered without regard to meals.
USE — Treatment of hypertension; treatment of symptomatic chronic stable angina, vasospastic (Prinzmetal's) angina (confirmed or suspected); prevention of hospitalization due to angina with documented CAD (limited to patients without heart failure or ejection fraction <40%)>10%: Cardiovascular: Peripheral edema (2% to 15% dose related)
1% to 10%:
Cardiovascular: Flushing (1% to 3%), palpitation (1% to 4%)
Central nervous system: Headache (7%; similar to placebo 8%), dizziness (1% to 3%), fatigue (4%), somnolence (1% to 2%)
Dermatologic: Rash (1% to 2%), pruritus (1% to 2%)
Endocrine & metabolic: Male sexual dysfunction (1% to 2%)
Gastrointestinal: Nausea (3%), abdominal pain (1% to 2%), dyspepsia (1% to 2%), gingival hyperplasia
Neuromuscular & skeletal: Muscle cramps (1% to 2%), weakness (1% to 2%)
Respiratory: Dyspnea (1% to 2%), pulmonary edema (15% from PRAISE trial, CHF population)
<1%>90%) to inactive metabolite
Bioavailability: 64% to 90%
Half-life elimination: 30-50 hours; increased with hepatic dysfunction
Time to peak, plasma: 6-12 hours
Excretion: Urine (10% as parent, 60% as metabolite)
PATIENT INFORMATION — Take as prescribed; do not stop abruptly without consulting prescriber. You may experience headache (if unrelieved, consult prescriber), nausea or vomiting (frequent small meals may help), or constipation (increased dietary bulk and fluids may help). May cause drowsiness; use caution when driving or engaging in tasks that require alertness until response to drug is known. Report unrelieved headache, vomiting, constipation, palpitations, peripheral or facial swelling, weight gain >5 lb/week, or respiratory changes.
Sunday, May 11, 2008
Amlexanox
U.S. BRAND NAMES — Aphthasol®
PHARMACOLOGIC CATEGORY
Anti-inflammatory, Locally Applied
DOSING: ADULTS — Aphthous ulcers: Topical: Administer (0.5 cm - 1/4") directly on ulcers 4 times/day following oral hygiene, after meals, and at bedtime.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Paste: 5% (5 g) [contains benzyl alcohol]
DOSAGE FORMS: CONCISE
Paste:
Aphthasol®: 5% (5 g)
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of aphthous ulcers (ie, canker sores)
USE - UNLABELED / INVESTIGATIONAL — Allergic disorders
ADVERSE REACTIONS SIGNIFICANT
1% to 2%:
Dermatologic: Allergic contact dermatitis
Gastrointestinal: Oral irritation
<1% (Limited to important or life-threatening): Contact mucositis
CONTRAINDICATIONS — Hypersensitivity to amlexanox or any component of the formulation
WARNINGS / PRECAUTIONS — Discontinue therapy if rash or contact mucositis develops.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Due to lack of data, avoid use in pregnancy, if possible.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Paste (Aphthasol)
5% (5): $23.20
MECHANISM OF ACTION — As a benzopyrano-bipyridine carboxylic acid derivative, amlexanox has anti-inflammatory and antiallergic properties; it inhibits chemical mediatory release of the slow-reacting substance of anaphylaxis (SRS-A) and may have antagonistic effects on interleukin-3
PHARMACODYNAMICS / KINETICS
Absorption: Some from swallowed paste
Metabolism: Hydroxylated and conjugated metabolites
Half-life elimination: 3.5 hours
Time to peak, serum: 2 hours
Excretion: Urine (17% as unchanged drug)
PHARMACOLOGIC CATEGORY
Anti-inflammatory, Locally Applied
DOSING: ADULTS — Aphthous ulcers: Topical: Administer (0.5 cm - 1/4") directly on ulcers 4 times/day following oral hygiene, after meals, and at bedtime.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Paste: 5% (5 g) [contains benzyl alcohol]
DOSAGE FORMS: CONCISE
Paste:
Aphthasol®: 5% (5 g)
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of aphthous ulcers (ie, canker sores)
USE - UNLABELED / INVESTIGATIONAL — Allergic disorders
ADVERSE REACTIONS SIGNIFICANT
1% to 2%:
Dermatologic: Allergic contact dermatitis
Gastrointestinal: Oral irritation
<1% (Limited to important or life-threatening): Contact mucositis
CONTRAINDICATIONS — Hypersensitivity to amlexanox or any component of the formulation
WARNINGS / PRECAUTIONS — Discontinue therapy if rash or contact mucositis develops.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Due to lack of data, avoid use in pregnancy, if possible.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Paste (Aphthasol)
5% (5): $23.20
MECHANISM OF ACTION — As a benzopyrano-bipyridine carboxylic acid derivative, amlexanox has anti-inflammatory and antiallergic properties; it inhibits chemical mediatory release of the slow-reacting substance of anaphylaxis (SRS-A) and may have antagonistic effects on interleukin-3
PHARMACODYNAMICS / KINETICS
Absorption: Some from swallowed paste
Metabolism: Hydroxylated and conjugated metabolites
Half-life elimination: 3.5 hours
Time to peak, serum: 2 hours
Excretion: Urine (17% as unchanged drug)
Amitriptyline and perphenazine
PHARMACOLOGIC CATEGORY
Antidepressant, Tricyclic (Tertiary Amine)
Antipsychotic Agent, Typical, Phenothiazine
DOSING: ADULTS — Depression and anxiety: Oral: 1 tablet 2-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Avoid use in severe hepatic failure.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
2-10: Amitriptyline hydrochloride 10 mg and perphenazine 2 mg
2-25: Amitriptyline hydrochloride 25 mg and perphenazine 2 mg
4-10: Amitriptyline hydrochloride 10 mg and perphenazine 4 mg
4-25: Amitriptyline hydrochloride 25 mg and perphenazine 4 mg
4-50: Amitriptyline hydrochloride 50 mg and perphenazine 4 mg
DOSAGE FORMS: CONCISE
Tablet:
Generics:
2-10: Amitriptyline 10 mg and perphenazine 2 mg
2-25: Amitriptyline 25 mg and perphenazine 2 mg
4-10: Amitriptyline 10 mg and perphenazine 4 mg
4-25: Amitriptyline 25 mg and perphenazine 4 mg
4-50: Amitriptyline 50 mg and perphenazine 4 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Treatment of patients with moderate to severe anxiety and depression
USE - UNLABELED / INVESTIGATIONAL — Depression with psychotic features
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to amitriptyline, perphenazine, or any component of the formulation (cross-sensitivity with other phenothiazines may exist); angle-closure glaucoma; bone marrow depression; severe liver or cardiac disease; pregnancy
WARNINGS / PRECAUTIONS
Based on the amitriptyline component:
Antidepressants increase the risk of suicidal thinking and behavior in children and adolescents with major depressive disorder (MDD) and other depressive disorders; consider risk prior to prescribing. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; the child's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. Such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits. Adults treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. A medication guide should be dispensed with each prescription.
The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Monitor for worsening of depression or suicidality, especially during initiation of therapy or with dose increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression occur.
May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder.
Often causes drowsiness/sedation, resulting in impaired performance of tasks requiring alertness (eg, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is very high relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May cause hyponatremia/SIADH. May increase the risks associated with electroconvulsive therapy. Consider discontinuing, when possible, prior to elective surgery.. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.
May cause orthostatic hypotension; the risk of this problem is very high relative to other antidepressants. Use with caution in patients at risk of hypotension or in patients where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). The degree of anticholinergic blockade produced by this agent is very high relative to other cyclic antidepressants; use with caution in patients with urinary retention, benign prostatic hyperplasia, narrow-angle glaucoma, xerostomia, visual problems, constipation, or a history of bowel obstruction. May alter glucose control - use with caution in patients with diabetes.
Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities). The risk of conduction abnormalities with this agent is high relative to other antidepressants. May lower seizure threshold - use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in hyperthyroid patients or those receiving thyroid supplementation. Use with caution in patients with hepatic or renal dysfunction and in elderly patients.
Based on the perphenazine component:
May cause hypotension. May be sedating; use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; predisposition to seizures; severe cardiac, hepatic, renal, or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (eg, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction - life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose).
Phenothiazines may cause anticholinergic effects (confusion, agitation, constipation, xerostomia, blurred vision, urinary retention); therefore, they should be used with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, xerostomia, or visual problems. Conditions which also may be exacerbated by cholinergic blockade include narrow-angle glaucoma (screening is recommended) and worsening of myasthenia gravis. Relative to other neuroleptics, perphenazine has a low potency of cholinergic blockade.
May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is moderate-high relative to other neuroleptics). Older patients are at increased risk for developing tardive dyskinesia. May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.
This combination is not FDA approved for use in children or for the treatment of bipolar depression.
RESTRICTIONS — An FDA-approved medication guide concerning the use of antidepressants in children and teenagers must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm. Dispense to parents or guardians of children and teenagers receiving this medication.
DRUG INTERACTIONS
Amitriptyline: Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak)
Perphenazine: Substrate of CYP1A2 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2D6 (weak)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (due to increased sedation).
PREGNANCY RISK FACTOR — D (show table)
LACTATION — Enters breast milk/contraindicated
PRICING — (data from drugstore.com)
Tablets (Perphenazine-Amitriptyline)
2-10 mg (60): $8.99
2-25 mg (30): $7.99
4-25 mg (60): $11.99
4-50 mg (60): $27.99
MONITORING PARAMETERS — Vital signs; lipid profile, fasting blood glucose/Hb A1c; BMI, weight; mental status, abnormal involuntary movement scale (AIMS), extrapyramidal symptoms (EPS)
CANADIAN BRAND NAMES — Etrafon®
INTERNATIONAL BRAND NAMES — Etrafon (CA); Mutabase (ES); Mutabon A (AE, BH, CY, EG, IL, IQ, IR, JO, LY, OM, QA, SA, SY); Mutabon D (AE, AR, BH, CL, CY, EG, ID, IL, IQ, IR, JO, LY, OM, PY, QA, SA, SY); Mutabon F (AE, BH, CY, EG, IL, IQ, IR, JO, LY, OM, QA, SA, SY); Mutabon M (AE, BH, CY, EG, ID, IL, IQ, IR, JO, LY, OM, QA, SA, SY); Mutabon-A (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Mutabon-D (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Mutabon-F (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Mutabon-M (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Neuragon-A (TH); Neuragon-B (TH); Polybon (TH); Triptafen (GB); Triptafen M (GB)
MECHANISM OF ACTION
Amitriptyline increases the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane.
Perphenazine is a piperazine phenothiazine antipsychotic which blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones.
PHARMACODYNAMICS / KINETICS — See individual agents.
Antidepressant, Tricyclic (Tertiary Amine)
Antipsychotic Agent, Typical, Phenothiazine
DOSING: ADULTS — Depression and anxiety: Oral: 1 tablet 2-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Avoid use in severe hepatic failure.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
2-10: Amitriptyline hydrochloride 10 mg and perphenazine 2 mg
2-25: Amitriptyline hydrochloride 25 mg and perphenazine 2 mg
4-10: Amitriptyline hydrochloride 10 mg and perphenazine 4 mg
4-25: Amitriptyline hydrochloride 25 mg and perphenazine 4 mg
4-50: Amitriptyline hydrochloride 50 mg and perphenazine 4 mg
DOSAGE FORMS: CONCISE
Tablet:
Generics:
2-10: Amitriptyline 10 mg and perphenazine 2 mg
2-25: Amitriptyline 25 mg and perphenazine 2 mg
4-10: Amitriptyline 10 mg and perphenazine 4 mg
4-25: Amitriptyline 25 mg and perphenazine 4 mg
4-50: Amitriptyline 50 mg and perphenazine 4 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Treatment of patients with moderate to severe anxiety and depression
USE - UNLABELED / INVESTIGATIONAL — Depression with psychotic features
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to amitriptyline, perphenazine, or any component of the formulation (cross-sensitivity with other phenothiazines may exist); angle-closure glaucoma; bone marrow depression; severe liver or cardiac disease; pregnancy
WARNINGS / PRECAUTIONS
Based on the amitriptyline component:
Antidepressants increase the risk of suicidal thinking and behavior in children and adolescents with major depressive disorder (MDD) and other depressive disorders; consider risk prior to prescribing. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; the child's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. Such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits. Adults treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. A medication guide should be dispensed with each prescription.
The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Monitor for worsening of depression or suicidality, especially during initiation of therapy or with dose increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression occur.
May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder.
Often causes drowsiness/sedation, resulting in impaired performance of tasks requiring alertness (eg, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is very high relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May cause hyponatremia/SIADH. May increase the risks associated with electroconvulsive therapy. Consider discontinuing, when possible, prior to elective surgery.. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.
May cause orthostatic hypotension; the risk of this problem is very high relative to other antidepressants. Use with caution in patients at risk of hypotension or in patients where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). The degree of anticholinergic blockade produced by this agent is very high relative to other cyclic antidepressants; use with caution in patients with urinary retention, benign prostatic hyperplasia, narrow-angle glaucoma, xerostomia, visual problems, constipation, or a history of bowel obstruction. May alter glucose control - use with caution in patients with diabetes.
Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities). The risk of conduction abnormalities with this agent is high relative to other antidepressants. May lower seizure threshold - use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in hyperthyroid patients or those receiving thyroid supplementation. Use with caution in patients with hepatic or renal dysfunction and in elderly patients.
Based on the perphenazine component:
May cause hypotension. May be sedating; use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; predisposition to seizures; severe cardiac, hepatic, renal, or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (eg, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction - life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose).
Phenothiazines may cause anticholinergic effects (confusion, agitation, constipation, xerostomia, blurred vision, urinary retention); therefore, they should be used with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, xerostomia, or visual problems. Conditions which also may be exacerbated by cholinergic blockade include narrow-angle glaucoma (screening is recommended) and worsening of myasthenia gravis. Relative to other neuroleptics, perphenazine has a low potency of cholinergic blockade.
May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is moderate-high relative to other neuroleptics). Older patients are at increased risk for developing tardive dyskinesia. May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.
This combination is not FDA approved for use in children or for the treatment of bipolar depression.
RESTRICTIONS — An FDA-approved medication guide concerning the use of antidepressants in children and teenagers must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm. Dispense to parents or guardians of children and teenagers receiving this medication.
DRUG INTERACTIONS
Amitriptyline: Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak)
Perphenazine: Substrate of CYP1A2 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2D6 (weak)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (due to increased sedation).
PREGNANCY RISK FACTOR — D (show table)
LACTATION — Enters breast milk/contraindicated
PRICING — (data from drugstore.com)
Tablets (Perphenazine-Amitriptyline)
2-10 mg (60): $8.99
2-25 mg (30): $7.99
4-25 mg (60): $11.99
4-50 mg (60): $27.99
MONITORING PARAMETERS — Vital signs; lipid profile, fasting blood glucose/Hb A1c; BMI, weight; mental status, abnormal involuntary movement scale (AIMS), extrapyramidal symptoms (EPS)
CANADIAN BRAND NAMES — Etrafon®
INTERNATIONAL BRAND NAMES — Etrafon (CA); Mutabase (ES); Mutabon A (AE, BH, CY, EG, IL, IQ, IR, JO, LY, OM, QA, SA, SY); Mutabon D (AE, AR, BH, CL, CY, EG, ID, IL, IQ, IR, JO, LY, OM, PY, QA, SA, SY); Mutabon F (AE, BH, CY, EG, IL, IQ, IR, JO, LY, OM, QA, SA, SY); Mutabon M (AE, BH, CY, EG, ID, IL, IQ, IR, JO, LY, OM, QA, SA, SY); Mutabon-A (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Mutabon-D (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Mutabon-F (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Mutabon-M (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Neuragon-A (TH); Neuragon-B (TH); Polybon (TH); Triptafen (GB); Triptafen M (GB)
MECHANISM OF ACTION
Amitriptyline increases the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane.
Perphenazine is a piperazine phenothiazine antipsychotic which blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones.
PHARMACODYNAMICS / KINETICS — See individual agents.
Amitriptyline and chlordiazepoxide
U.S. BRAND NAMES — Limbitrol® DS; Limbitrol®
PHARMACOLOGIC CATEGORY
Antidepressant, Tricyclic (Tertiary Amine)
Benzodiazepine
DOSING: ADULTS — Depression and anxiety: Oral: Initial: 3-4 tablets in divided doses; this may be increased to 6 tablets/day as required. Some patients respond to smaller doses and can be maintained on 2 tablets.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 12.5/5: Amitriptyline hydrochloride 12.5 mg and chlordiazepoxide 5 mg; 25/10: Amitriptyline hydrochloride 25 mg and chlordiazepoxide 10 mg
Limbitrol®: 12.5/5: Amitriptyline hydrochloride 12.5 mg and chlordiazepoxide 5 mg
Limbitrol® DS: 25/10: Amitriptyline hydrochloride 25 mg and chlordiazepoxide 10 mg
DOSAGE FORMS: CONCISE
Tablet: 12.5/5: Amitriptyline 12.5 mg and chlordiazepoxide 5 mg; 25/10: Amitriptyline 25 mg and chlordiazepoxide 10 mg
Limbitrol®: 12.5/5: Amitriptyline 12.5 mg and chlordiazepoxide 5 mg
Limbitrol® DS: 25/10: Amitriptyline 25 mg and chlordiazepoxide 10 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Treatment of moderate to severe anxiety and/or agitation and depression
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to benzodiazepines, tricyclic antidepressants, or any component of the formulation; depression of CNS; MAO inhibitors; acute recovery phase following MI; angle-closure glaucoma; pregnancy
WARNINGS / PRECAUTIONS
Based on amitriptyline component:
Antidepressants increase the risk of suicidal thinking and behavior in children and adolescents with major depressive disorder (MDD) and other depressive disorders; consider risk prior to prescribing. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; the child's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. Such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits. Adults treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. A medication guide should be dispensed with each prescription.
The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Monitor for worsening of depression or suicidality, especially during initiation of therapy or with dose increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression occur.
May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder.
Often causes drowsiness/sedation, resulting in impaired performance of tasks requiring alertness (eg, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is very high relative to other antidepressants. May cause hyponatremia/SIADH. May increase the risks associated with electroconvulsive therapy. Consider discontinuing, when possible, prior to elective surgery. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.
May cause orthostatic hypotension; the risk of this problem is very high relative to other antidepressants. Use with caution in patients at risk of hypotension or in patients where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). The degree of anticholinergic blockade produced by this agent is very high relative to other cyclic antidepressants; use with caution in patients with urinary retention, benign prostatic hyperplasia, narrow-angle glaucoma, xerostomia, visual problems, constipation, or a history of bowel obstruction. May alter glucose control - use with caution in patients with diabetes.
Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities). The risk of conduction abnormalities with this agent is high relative to other antidepressants. May lower seizure threshold - use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in hyperthyroid patients or those receiving thyroid supplementation. Use with caution in patients with hepatic or renal dysfunction and in elderly patients.
Based on chlordiazepoxide component:
Active metabolites with extended half-lives may lead to delayed accumulation and adverse effects. Use with caution in elderly or debilitated patients, pediatric patients, patients with hepatic disease (including alcoholics) or renal impairment. Use with caution in patients with respiratory disease or impaired gag reflex. Use with caution in patients with porphyria.
Parenteral administration should be avoided in comatose patients or shock. Adequate resuscitative equipment/personnel should be available, and appropriate monitoring should be conducted at the time of injection and for several hours following administration. The parenteral formulation should be diluted for I.M. administration with the supplied diluent only. This diluent should not be used when preparing the drug for intravenous administration.
Causes CNS depression (dose related) resulting in sedation, dizziness, confusion, or ataxia which may impair physical and mental capabilities. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive agents (lithium, phenothiazines). Effects with other sedative drugs or ethanol may be potentiated. Benzodiazepines have been associated with falls and traumatic injury and should be used with extreme caution in patients who are at risk of these events (especially the elderly).
Use caution in patients with depression, particularly if suicidal risk may be present. Use with caution in patients with a history of drug dependence. Benzodiazepines have been associated with dependence and acute withdrawal symptoms on discontinuation or reduction in dose. Acute withdrawal, including seizures, may be precipitated after administration of flumazenil to patients receiving long-term benzodiazepine therapy.
Benzodiazepines have been associated with anterograde amnesia. Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients. Does not have analgesic, antidepressant, or antipsychotic properties.
Amitriptyline and chlordiazepoxide combination is FDA approved for depression associated with anxiety in children 12 years of age. This combination is not FDA approved for the treatment of bipolar depression.
RESTRICTIONS — C-IV
An FDA-approved medication guide concerning the use of antidepressants in children and teenagers must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm. Dispense to parents or guardians of children and teenagers receiving this medication.
DRUG INTERACTIONS
Amitriptyline: Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak)
Chlordiazepoxide: Substrate of CYP3A4 (major)
Also see individual agents.
PREGNANCY RISK FACTOR — D (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
PRICING — (data from drugstore.com)
Tablets (Chlordiazepoxide-Amitriptyline)
5-12.5 mg (60): $38.12
Tablets (Limbitrol DS)
10-25 mg (60): $109.99
CANADIAN BRAND NAMES — Limbitrol®
INTERNATIONAL BRAND NAMES — Limbatril (DE); Limbatrilin (CL); Limbitrol (AE, AT, BH, BR, CA, CY, EG, FI, FR, GB, GH, GR, ID, IE, IQ, IR, JO, KE, KW, LB, LY, NL, OM, QA, SA, SY, TW, TZ, UG, YE, ZA, ZM); Limbitrol F (ZA); Limbitryl (IT)
MECHANISM OF ACTION — See individual agents.
PHARMACODYNAMICS / KINETICS — See individual agents.
PHARMACOLOGIC CATEGORY
Antidepressant, Tricyclic (Tertiary Amine)
Benzodiazepine
DOSING: ADULTS — Depression and anxiety: Oral: Initial: 3-4 tablets in divided doses; this may be increased to 6 tablets/day as required. Some patients respond to smaller doses and can be maintained on 2 tablets.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 12.5/5: Amitriptyline hydrochloride 12.5 mg and chlordiazepoxide 5 mg; 25/10: Amitriptyline hydrochloride 25 mg and chlordiazepoxide 10 mg
Limbitrol®: 12.5/5: Amitriptyline hydrochloride 12.5 mg and chlordiazepoxide 5 mg
Limbitrol® DS: 25/10: Amitriptyline hydrochloride 25 mg and chlordiazepoxide 10 mg
DOSAGE FORMS: CONCISE
Tablet: 12.5/5: Amitriptyline 12.5 mg and chlordiazepoxide 5 mg; 25/10: Amitriptyline 25 mg and chlordiazepoxide 10 mg
Limbitrol®: 12.5/5: Amitriptyline 12.5 mg and chlordiazepoxide 5 mg
Limbitrol® DS: 25/10: Amitriptyline 25 mg and chlordiazepoxide 10 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Treatment of moderate to severe anxiety and/or agitation and depression
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to benzodiazepines, tricyclic antidepressants, or any component of the formulation; depression of CNS; MAO inhibitors; acute recovery phase following MI; angle-closure glaucoma; pregnancy
WARNINGS / PRECAUTIONS
Based on amitriptyline component:
Antidepressants increase the risk of suicidal thinking and behavior in children and adolescents with major depressive disorder (MDD) and other depressive disorders; consider risk prior to prescribing. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; the child's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. Such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits. Adults treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. A medication guide should be dispensed with each prescription.
The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Monitor for worsening of depression or suicidality, especially during initiation of therapy or with dose increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression occur.
May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder.
Often causes drowsiness/sedation, resulting in impaired performance of tasks requiring alertness (eg, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is very high relative to other antidepressants. May cause hyponatremia/SIADH. May increase the risks associated with electroconvulsive therapy. Consider discontinuing, when possible, prior to elective surgery. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.
May cause orthostatic hypotension; the risk of this problem is very high relative to other antidepressants. Use with caution in patients at risk of hypotension or in patients where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). The degree of anticholinergic blockade produced by this agent is very high relative to other cyclic antidepressants; use with caution in patients with urinary retention, benign prostatic hyperplasia, narrow-angle glaucoma, xerostomia, visual problems, constipation, or a history of bowel obstruction. May alter glucose control - use with caution in patients with diabetes.
Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities). The risk of conduction abnormalities with this agent is high relative to other antidepressants. May lower seizure threshold - use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in hyperthyroid patients or those receiving thyroid supplementation. Use with caution in patients with hepatic or renal dysfunction and in elderly patients.
Based on chlordiazepoxide component:
Active metabolites with extended half-lives may lead to delayed accumulation and adverse effects. Use with caution in elderly or debilitated patients, pediatric patients, patients with hepatic disease (including alcoholics) or renal impairment. Use with caution in patients with respiratory disease or impaired gag reflex. Use with caution in patients with porphyria.
Parenteral administration should be avoided in comatose patients or shock. Adequate resuscitative equipment/personnel should be available, and appropriate monitoring should be conducted at the time of injection and for several hours following administration. The parenteral formulation should be diluted for I.M. administration with the supplied diluent only. This diluent should not be used when preparing the drug for intravenous administration.
Causes CNS depression (dose related) resulting in sedation, dizziness, confusion, or ataxia which may impair physical and mental capabilities. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive agents (lithium, phenothiazines). Effects with other sedative drugs or ethanol may be potentiated. Benzodiazepines have been associated with falls and traumatic injury and should be used with extreme caution in patients who are at risk of these events (especially the elderly).
Use caution in patients with depression, particularly if suicidal risk may be present. Use with caution in patients with a history of drug dependence. Benzodiazepines have been associated with dependence and acute withdrawal symptoms on discontinuation or reduction in dose. Acute withdrawal, including seizures, may be precipitated after administration of flumazenil to patients receiving long-term benzodiazepine therapy.
Benzodiazepines have been associated with anterograde amnesia. Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients. Does not have analgesic, antidepressant, or antipsychotic properties.
Amitriptyline and chlordiazepoxide combination is FDA approved for depression associated with anxiety in children 12 years of age. This combination is not FDA approved for the treatment of bipolar depression.
RESTRICTIONS — C-IV
An FDA-approved medication guide concerning the use of antidepressants in children and teenagers must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm. Dispense to parents or guardians of children and teenagers receiving this medication.
DRUG INTERACTIONS
Amitriptyline: Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak)
Chlordiazepoxide: Substrate of CYP3A4 (major)
Also see individual agents.
PREGNANCY RISK FACTOR — D (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
PRICING — (data from drugstore.com)
Tablets (Chlordiazepoxide-Amitriptyline)
5-12.5 mg (60): $38.12
Tablets (Limbitrol DS)
10-25 mg (60): $109.99
CANADIAN BRAND NAMES — Limbitrol®
INTERNATIONAL BRAND NAMES — Limbatril (DE); Limbatrilin (CL); Limbitrol (AE, AT, BH, BR, CA, CY, EG, FI, FR, GB, GH, GR, ID, IE, IQ, IR, JO, KE, KW, LB, LY, NL, OM, QA, SA, SY, TW, TZ, UG, YE, ZA, ZM); Limbitrol F (ZA); Limbitryl (IT)
MECHANISM OF ACTION — See individual agents.
PHARMACODYNAMICS / KINETICS — See individual agents.
Amitriptyline
PHARMACOLOGIC CATEGORY
Antidepressant, Tricyclic (Tertiary Amine)
DOSING: ADULTS
Depression: Oral: 50-150 mg/day single dose at bedtime or in divided doses; dose may be gradually increased up to 300 mg/day.
Chronic pain management (unlabeled use): Oral: Initial: 25 mg at bedtime; may increase as tolerated to 100 mg/day.
Migraine prophylaxis (unlabeled use): Oral: Initial: 10-25 mg at bedtime; usual dose: 150 mg; reported dosing ranges: 10-400 mg/day
DOSING: PEDIATRIC
(For additional information see "Amitriptyline: Pediatric drug information")
Chronic pain management (unlabeled use): Oral: Initial: 0.1 mg/kg at bedtime, may advance as tolerated over 2-3 weeks to 0.5-2 mg/kg at bedtime
Depressive disorders:
Children (unlabeled use): Oral: Initial doses of 1 mg/kg/day given in 3 divided doses with increases to 1.5 mg/kg/day have been reported in a small number of children (n=9) 9-12 years of age; clinically, doses up to 3 mg/kg/day (5 mg/kg/day if monitored closely) have been proposed
Adolescents: Initial: 25-50 mg/day; may administer in divided doses; increase gradually to 100 mg/day in divided doses.
Migraine prophylaxis (unlabeled use): Oral: Initial: 0.25 mg/kg/day, given at bedtime; increase dose by 0.25 mg/kg/day to maximum 1 mg/kg/day. Reported dosing ranges: 0.1-2 mg/kg/day; maximum suggested dose: 10 mg.
DOSING: ELDERLY — Depression: Oral: Initial: 10-25 mg at bedtime; dose should be increased in 10-25 mg increments every week if tolerated; dose range: 25-150 mg/day. See Renal/Hepatic Impairment.
DOSING: RENAL IMPAIRMENT — Nondialyzable
DOSING: HEPATIC IMPAIRMENT — Use with caution and monitor plasma levels and patient response.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
DOSAGE FORMS: CONCISE
Tablet: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of symptoms of depression
USE - UNLABELED / INVESTIGATIONAL — Analgesic for certain chronic and neuropathic pain; prophylaxis against migraine headaches; treatment of depressive disorders in children
ADVERSE REACTIONS SIGNIFICANT — Anticholinergic effects may be pronounced; moderate to marked sedation can occur (tolerance to these effects usually occurs).
Frequency not defined.
Cardiovascular: Orthostatic hypotension, tachycardia, ECG changes (nonspecific), AV conduction changes, cardiomyopathy (rare), MI, stroke, heart block, arrhythmia, syncope, hypertension, palpitation
Central nervous system: Restlessness, dizziness, insomnia, sedation, fatigue, anxiety, cognitive function impaired, seizure, extrapyramidal symptoms, coma, hallucinations, confusion, disorientation, coordination impaired, ataxia, headache, nightmares, hyperpyrexia
Dermatologic: Allergic rash, urticaria, photosensitivity, alopecia
Endocrine & metabolic: Syndrome of inappropriate ADH secretion
Gastrointestinal: Weight gain, xerostomia, constipation, paralytic ileus, nausea, vomiting, anorexia, stomatitis, peculiar taste, diarrhea, black tongue
Genitourinary: Urinary retention
Hematologic: Bone marrow depression, purpura, eosinophilia
Neuromuscular & skeletal: Numbness, paresthesia, peripheral neuropathy, tremor, weakness
Ocular: Blurred vision, mydriasis, ocular pressure increased
Otic: Tinnitus
Miscellaneous: Diaphoresis, withdrawal reactions (nausea, headache, malaise)
Postmarketing and/or case reports: Neuroleptic malignant syndrome (rare), serotonin syndrome (rare)
CONTRAINDICATIONS — Hypersensitivity to amitriptyline or any component of the formulation (cross-sensitivity with other tricyclics may occur); use of MAO inhibitors within past 14 days; acute recovery phase following myocardial infarction; concurrent use of cisapride
WARNINGS / PRECAUTIONS — [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children and adolescents with major depressive disorder (MDD) and other depressive disorders; consider risk prior to prescribing. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; the child's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. Such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits. Adults treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. A medication guide should be dispensed with each prescription. Amitriptyline is not FDA-approved for use in children <12>0.5 mcg/mL; plasma levels do not always correlate with clinical effectiveness
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, ventricular tachycardia, and seizures. Following initiation of essential overdose management, toxic symptoms should be treated. Sodium bicarbonate is indicated when the QRS interval is >0.10 seconds or the QTc is >0.42 seconds. Ventricular arrhythmias often respond to phenytoin 15-20 mg/kg (adults) with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.). Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V. followed by a titrated infusion. Physostigmine (1-2 mg slow I.V. for adults or 0.5 mg slow I.V. for children) may be indicated in reversing cardiac arrhythmias that are due to vagal blockade, or for anticholinergic effects, but should only be used as a last measure in life-threatening situations. Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required.
CANADIAN BRAND NAMES — Apo-Amitriptyline®; Levate®; Novo-Triptyn; PMS-Amitriptyline
INTERNATIONAL BRAND NAMES — Adepril (IT); Amilit (IT); Amineurin (DE); Amiplin (TW); Amiprin (JP); Amitrip (NZ); Amitriptylinum (PL); Amytril (BR); Anapsique (MX); Antalin (CL); Apo-Amitriptyline (CA); Domical (GB); Elatrol (IL); Elatrolet (IL); Elavil (FR); Enafon (KR); Endep (AU); Lantron (JP); Laroxyl (BF, BJ, CI, ET, FR, GH, GM, GN, IT, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Levate (CA); Miketorin (JP); Neurotol (PY); Novo-Triptyn (CA); Novoprotect (DE); Pinsaun (TW); PMS-Amitriptyline (CA); Protanol (BR); Qualitriptine (HK); Redomex (BE); Sarotard (KR); Saroten (BF, BJ, CH, CI, CY, DE, DK, EE, ET, FI, GH, GM, GN, GR, IR, KE, LR, MA, ML, MR, MU, MW, NE, NG, PT, SC, SD, SE, SL, SN, TZ, UG, ZA, ZM, ZW); Saroten Retard (MY); Sarotena (IN); Sarotex (NL, NO, UY); Syneudon (DE); Teperin (HU, IQ, JO); Trepiline (ZA); Tridep (BG); Tripta (MY, TH); Triptizol (IT); Trynol (TW); Tryptal (IL); Tryptanol (AR, BR, EC, JP, MX, PE, TH, ZA); Tryptizol (AT, BE, CH, DK, EG, ES, GB, NL, NO, PT, SE); Trytomer (IN); Uxen (AR)
MECHANISM OF ACTION — Increases the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane
PHARMACODYNAMICS / KINETICS
Onset of action: Migraine prophylaxis: 6 weeks, higher dosage may be required in heavy smokers because of increased metabolism; Depression: 4-6 weeks, reduce dosage to lowest effective level
Distribution: Crosses placenta; enters breast milk
Metabolism: Hepatic to nortriptyline (active), hydroxy and conjugated derivatives; may be impaired in the elderly
Half-life elimination: Adults: 9-27 hours (average: 15 hours)
Time to peak, serum: ~4 hours
Excretion: Urine (18% as unchanged drug); feces (small amounts)
PATIENT INFORMATION — Do not discontinue medication abruptly. Full effect may not occur for 3-6 weeks. Avoid alcohol. May cause urine to turn blue-green. May cause drowsiness. Dry mouth may be helped by sips of water, sugarless gum, or hard candy.
Antidepressant, Tricyclic (Tertiary Amine)
DOSING: ADULTS
Depression: Oral: 50-150 mg/day single dose at bedtime or in divided doses; dose may be gradually increased up to 300 mg/day.
Chronic pain management (unlabeled use): Oral: Initial: 25 mg at bedtime; may increase as tolerated to 100 mg/day.
Migraine prophylaxis (unlabeled use): Oral: Initial: 10-25 mg at bedtime; usual dose: 150 mg; reported dosing ranges: 10-400 mg/day
DOSING: PEDIATRIC
(For additional information see "Amitriptyline: Pediatric drug information")
Chronic pain management (unlabeled use): Oral: Initial: 0.1 mg/kg at bedtime, may advance as tolerated over 2-3 weeks to 0.5-2 mg/kg at bedtime
Depressive disorders:
Children (unlabeled use): Oral: Initial doses of 1 mg/kg/day given in 3 divided doses with increases to 1.5 mg/kg/day have been reported in a small number of children (n=9) 9-12 years of age; clinically, doses up to 3 mg/kg/day (5 mg/kg/day if monitored closely) have been proposed
Adolescents: Initial: 25-50 mg/day; may administer in divided doses; increase gradually to 100 mg/day in divided doses.
Migraine prophylaxis (unlabeled use): Oral: Initial: 0.25 mg/kg/day, given at bedtime; increase dose by 0.25 mg/kg/day to maximum 1 mg/kg/day. Reported dosing ranges: 0.1-2 mg/kg/day; maximum suggested dose: 10 mg.
DOSING: ELDERLY — Depression: Oral: Initial: 10-25 mg at bedtime; dose should be increased in 10-25 mg increments every week if tolerated; dose range: 25-150 mg/day. See Renal/Hepatic Impairment.
DOSING: RENAL IMPAIRMENT — Nondialyzable
DOSING: HEPATIC IMPAIRMENT — Use with caution and monitor plasma levels and patient response.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
DOSAGE FORMS: CONCISE
Tablet: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of symptoms of depression
USE - UNLABELED / INVESTIGATIONAL — Analgesic for certain chronic and neuropathic pain; prophylaxis against migraine headaches; treatment of depressive disorders in children
ADVERSE REACTIONS SIGNIFICANT — Anticholinergic effects may be pronounced; moderate to marked sedation can occur (tolerance to these effects usually occurs).
Frequency not defined.
Cardiovascular: Orthostatic hypotension, tachycardia, ECG changes (nonspecific), AV conduction changes, cardiomyopathy (rare), MI, stroke, heart block, arrhythmia, syncope, hypertension, palpitation
Central nervous system: Restlessness, dizziness, insomnia, sedation, fatigue, anxiety, cognitive function impaired, seizure, extrapyramidal symptoms, coma, hallucinations, confusion, disorientation, coordination impaired, ataxia, headache, nightmares, hyperpyrexia
Dermatologic: Allergic rash, urticaria, photosensitivity, alopecia
Endocrine & metabolic: Syndrome of inappropriate ADH secretion
Gastrointestinal: Weight gain, xerostomia, constipation, paralytic ileus, nausea, vomiting, anorexia, stomatitis, peculiar taste, diarrhea, black tongue
Genitourinary: Urinary retention
Hematologic: Bone marrow depression, purpura, eosinophilia
Neuromuscular & skeletal: Numbness, paresthesia, peripheral neuropathy, tremor, weakness
Ocular: Blurred vision, mydriasis, ocular pressure increased
Otic: Tinnitus
Miscellaneous: Diaphoresis, withdrawal reactions (nausea, headache, malaise)
Postmarketing and/or case reports: Neuroleptic malignant syndrome (rare), serotonin syndrome (rare)
CONTRAINDICATIONS — Hypersensitivity to amitriptyline or any component of the formulation (cross-sensitivity with other tricyclics may occur); use of MAO inhibitors within past 14 days; acute recovery phase following myocardial infarction; concurrent use of cisapride
WARNINGS / PRECAUTIONS — [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children and adolescents with major depressive disorder (MDD) and other depressive disorders; consider risk prior to prescribing. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; the child's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. Such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits. Adults treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. A medication guide should be dispensed with each prescription. Amitriptyline is not FDA-approved for use in children <12>0.5 mcg/mL; plasma levels do not always correlate with clinical effectiveness
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, ventricular tachycardia, and seizures. Following initiation of essential overdose management, toxic symptoms should be treated. Sodium bicarbonate is indicated when the QRS interval is >0.10 seconds or the QTc is >0.42 seconds. Ventricular arrhythmias often respond to phenytoin 15-20 mg/kg (adults) with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.). Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V. followed by a titrated infusion. Physostigmine (1-2 mg slow I.V. for adults or 0.5 mg slow I.V. for children) may be indicated in reversing cardiac arrhythmias that are due to vagal blockade, or for anticholinergic effects, but should only be used as a last measure in life-threatening situations. Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required.
CANADIAN BRAND NAMES — Apo-Amitriptyline®; Levate®; Novo-Triptyn; PMS-Amitriptyline
INTERNATIONAL BRAND NAMES — Adepril (IT); Amilit (IT); Amineurin (DE); Amiplin (TW); Amiprin (JP); Amitrip (NZ); Amitriptylinum (PL); Amytril (BR); Anapsique (MX); Antalin (CL); Apo-Amitriptyline (CA); Domical (GB); Elatrol (IL); Elatrolet (IL); Elavil (FR); Enafon (KR); Endep (AU); Lantron (JP); Laroxyl (BF, BJ, CI, ET, FR, GH, GM, GN, IT, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Levate (CA); Miketorin (JP); Neurotol (PY); Novo-Triptyn (CA); Novoprotect (DE); Pinsaun (TW); PMS-Amitriptyline (CA); Protanol (BR); Qualitriptine (HK); Redomex (BE); Sarotard (KR); Saroten (BF, BJ, CH, CI, CY, DE, DK, EE, ET, FI, GH, GM, GN, GR, IR, KE, LR, MA, ML, MR, MU, MW, NE, NG, PT, SC, SD, SE, SL, SN, TZ, UG, ZA, ZM, ZW); Saroten Retard (MY); Sarotena (IN); Sarotex (NL, NO, UY); Syneudon (DE); Teperin (HU, IQ, JO); Trepiline (ZA); Tridep (BG); Tripta (MY, TH); Triptizol (IT); Trynol (TW); Tryptal (IL); Tryptanol (AR, BR, EC, JP, MX, PE, TH, ZA); Tryptizol (AT, BE, CH, DK, EG, ES, GB, NL, NO, PT, SE); Trytomer (IN); Uxen (AR)
MECHANISM OF ACTION — Increases the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane
PHARMACODYNAMICS / KINETICS
Onset of action: Migraine prophylaxis: 6 weeks, higher dosage may be required in heavy smokers because of increased metabolism; Depression: 4-6 weeks, reduce dosage to lowest effective level
Distribution: Crosses placenta; enters breast milk
Metabolism: Hepatic to nortriptyline (active), hydroxy and conjugated derivatives; may be impaired in the elderly
Half-life elimination: Adults: 9-27 hours (average: 15 hours)
Time to peak, serum: ~4 hours
Excretion: Urine (18% as unchanged drug); feces (small amounts)
PATIENT INFORMATION — Do not discontinue medication abruptly. Full effect may not occur for 3-6 weeks. Avoid alcohol. May cause urine to turn blue-green. May cause drowsiness. Dry mouth may be helped by sips of water, sugarless gum, or hard candy.
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