Adult: Usual dose: 100-200 mg daily. For severely ill patients: Dosage may be further increased gradually to 300 mg daily if necessary. Initiate therapy at a lower level and increase according to tolerance and clinical response. Initial therapy may be administered as a single daily dose or in divided doses and maintenance may be given on a once-daily schedule. Elderly: Usual dose: 25-100 mg daily. For severely ill patients: Dosage may be further increased to 150 mg daily. Initiate therapy at a lower level and increase according to tolerance and clinical response. Initial therapy may be administered as a single daily dose or in divided doses and maintenance may be given on a once-daily schedule. Child: Adolescents Usual dose: 25-100 mg daily. For severely ill patients: Dosage may be further increased to 150 mg daily. Initiate therapy at a lower level and increase according to tolerance and clinical response. Initial therapy may be administered as a single daily dose or in divided doses and maintenance may be given on a once-daily schedule.
Nhóm bệnh nhân đặc biệt
Pharmacogenomics:
Desipramine is hydroxylated by CYP2D6 to an inactive metabolite, 2-hydroxydesipramine. Interindividual differences in pharmacokinetic parameters and treatment outcomes associated with CYP2D6 genetic variation have been observed. Individuals with reduced CYP2D6 enzyme activity, known as CYP2D6 poor metabolisers, may have higher than expected plasma concentrations of desipramine, and an increased risk of adverse effects (e.g. confusion, marked sedation) when given typical doses. Available data show that approx 7-10% of Caucasians are CYP2D6 poor metabolisers. Genetic testing for CYP2D6 may be considered to help clinicians optimise the treatment initiation of desipramine.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of December 2016:
Phenotype and Genotype
Implications
Recommendations
CYP2D6 ultrarapid metabolisers
Individuals carrying duplications of functional alleles (e.g. (*1/*1)xN, (*1/*2)xN, (*2/*2)xN) with an activity score of
>2.0
Increased metabolism of desipramine, resulting in lower plasma concentrations and increased probability of pharmacotherapy failure.
Avoid use and consider alternative drugs not metabolised by CYP2D6. Consider titrating to a higher target dose if TCA use is necessary. Subsequent dose adjustments may be guided by therapeutic drug monitoring.
CYP2D6 normal metabolisers
Individuals carrying 2 normal function alleles, or 2 decreased function alleles, or 1 normal and no function allele, or 1 normal and decreased function allele, or combinations of duplicated alleles (e.g. *1/*1, *1/*2, *2/*2, *1/*9, *1/*41, *41/*41, *1/*5, *1/*4) with an activity score of 1.0-2.0
Normal metabolism.
Initiate therapy with the recommended starting dose.
CYP2D6 intermediate metabolisers
Individuals carrying 1 decreased function and 1 no function allele (e.g. *4/*41, *5/*9, *4/*10) with an activity score of 0.5) with an activity score of 0.5
Reduced metabolism of desipramine, resulting in higher plasma concentrations and increased risk of adverse effects.
Consider a 25% reduction of the recommended starting dose. Subsequent dose adjustments may be guided by therapeutic drug monitoring.
CYP2D6 poor metabolisers
Individuals carrying only no function alleles (e.g. *4/*4, (*4/*4)xN, *3/*4, *5/*5, *5/*6) with an activity score of 0
Significantly reduced metabolism of desipramine, resulting in higher plasma concentrations and increased adverse effects.
Avoid use and consider alternative drugs not metabolised by CYP2D6. Consider a 50% reduction of recommended starting dose if TCA use is necessary. Subsequent dose adjustments may be guided by therapeutic drug monitoring.
Cách dùng
May be taken with or without food.
Chống chỉ định
Acute recovery period following MI. Use of MAOIs (concurrently or within 14 days of stopping desipramine or MAOI) for psychiatric disorders; concurrent use with linezolid or IV methylthioninium chloride.
Thận trọng
Patient with CV disease, family history of sudden death, cardiac dysrhythmias, or cardiac conduction disturbances, thyroid disease, decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, visual problems (including patients who have not had an iridectomy for narrow-angle glaucoma risk factors), diabetes, and those at risk of seizures (including history of seizures, head trauma, brain damage, alcoholism). Discontinue prior to elective surgery. Not indicated for the treatment of bipolar disorder. Avoid abrupt withdrawal. Hepatic and renal impairment. Adolescents and elderly. Pregnancy and lactation.
Tác dụng không mong muốn
Significant: Pupillary dilation, elevation and lowering of blood sugar levels, anticholinergic effects (e.g. constipation, xerostomia, blurred vision, urinary retention). Blood and lymphatic system disorders: Bone marrow depression (including agranulocytosis, eosinophilia, purpura, thrombocytopenia). Cardiac disorders: Palpitations, heart block, arrhythmias, premature ventricular contractions, tachycardia, ventricular fibrillation. Ear and labyrinth disorders: Tinnitus. Eye disorders: Disturbance of accommodation, mydriasis, increased IOP. Gastrointestinal disorders: Nausea, vomiting, epigastric distress, peculiar taste, abdominal cramps, diarrhoea, stomatitis, black tongue, paralytic ileus, parotid swelling. General disorders and administration site conditions: Proneness to falling, weakness, fatigue, fever. Hepatobiliary disorders: Hepatitis, jaundice. Investigations: Elevated LFT, altered liver function, increased pancreatic enzymes, alterations in EEG patterns, weight gain or loss, elevated alkaline phosphatase. Metabolism and nutrition disorders: Anorexia, SIADH. Nervous system disorders: Numbness, tingling, paraesthesia of extremities, drowsiness, dizziness, headache, incoordination, ataxia, tremors, peripheral neuropathy, extrapyramidal symptoms, seizures, NMS. Psychiatric disorders: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions, anxiety, restlessness, agitation, insomnia, nightmares, hypomania, exacerbation of psychosis. Renal and urinary disorders: Delayed micturition, dilation of urinary tract, urinary frequency, nocturia. Reproductive system and breast disorders: Gynaecomastia in males, breast enlargement and galactorrhoea in females; increased or decreased libido, impotence, painful ejaculation, testicular swelling. Skin and subcutaneous tissue disorders: Rash, petechiae, urticaria, itching, photosensitisation, perspiration, alopecia. Vascular disorders: Hypotension, hypertension, flushing. Potentially Fatal: Serotonin syndrome, suicidal thinking and behaviour.
Thông tin tư vấn bệnh nhân
This drug may cause CNS depression, if affected, do not drive or operate machinery.
Chỉ số theo dõi
Assess for suicidal tendencies before and during initiation of therapy or following an increase or decrease of dosage; cardiac and seizure history prior to initiating therapy. Observe closely for clinical worsening, suicidality, or unusual changes in behaviour.
Quá liều
Symptoms: Cardiac dysrhythmias, severe hypotension, convulsions, CNS depression (including coma), changes in the ECG (particularly in QRS axis or width), confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia. Management: Aggressive supportive treatment and serum alkalinisation. General: Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient’s airway, establish an IV line, and initiate gastric decontamination. Cardiac monitoring and observation (minimum of 6 hours) for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary; continue monitoring if signs of toxicity occur at any time during this period. Gastrointestinal decontamination: Administer activated charcoal to patients who present early after an overdose. CV: Initiate serum alkalinisation with IV Na bicarbonate and hyperventilation (as needed) in patients manifesting significant toxicity (e.g. QRS widening). CNS: In patients with CNS depression, early intubation is advised. Benzodiazepines can be given to control seizures; if ineffective or if seizures recur, other anticonvulsants (e.g. phenobarbital, propofol) may be used.
Tương tác
May block the antihypertensive effect of guanethidine and similarly acting compounds. Additive sedative effects with benzodiazepines (e.g. chlordiazepoxide, diazepam). Increased plasma concentrations with cimetidine. Decreased plasma concentrations with barbiturates. Increased risk of serotonin syndrome with other serotonergic drugs (e.g. triptans, other TCAs, fentanyl, lithium, tramadol, buspirone, tryptophan). Potentially Fatal: Risk of serotonin syndrome with MAOIs, including linezolid and IV methylthioninium chloride.
Tương tác với thức ăn
May enhance the CNS depressant effects of alcohol. Increased risk of serotonin syndrome with St. John's wort.
Ảnh hưởng đến kết quả xét nghiệm
May cause false-positive results with urine detection of amphetamines/methamphetamines.
Tác dụng
Description: Mechanism of Action: Desipramine is a dibenzazepine-derivative TCA that is the active metabolite of imipramine. The exact mechanism for its antidepressant activity is unknown; however, it is postulated to increase the synaptic concentration of norepinephrine (and serotonin, to a lesser extent) by blocking their reuptake from the presynaptic neuronal membrane. Additional receptor effects have also been found including desensitisation of adenyl cyclase and down regulation of β-adrenergic and serotonin receptors. Onset: Depression: Within 1-2 weeks. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: 38%. Time to peak plasma concentration: 4-6 hours. Distribution: Enters breast milk. Metabolism: Metabolised in the liver mainly via oxidation to 2-hydroxydesipramine. Excretion: Via urine (approx 70%). Elimination half-life: 7->60 hours.
Đặc tính
Desipramine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2995, Desipramine. https://pubchem.ncbi.nlm.nih.gov/compound/Desipramine. Accessed Mar. 28, 2023.
Bảo quản
Store between 20-25°C. Protect from excessive heat.
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