ImipraminIndikasi: Imipramin dapat digunakan pada berbagai bentuk depresi dan juga enuresis pada anak-anak. Obat ini juga dapat digunakan pada tatalaksana nyeri kronik pada orang dewasa, profilaksis nyeri kepala vaskuler, cluster headache, dan insomnia.

Mekanisme aksi: Mekanisme imipramin tidak sepenuhnya diketahui. Akan tetapi, imipramin diketahui tidak secara langsung menstimulasi sistem saraf pusat. Efek klinis ini dihipotesiskan sebagai akibat potensiasi dari sinaps adrenergik dengan memblok ambilan kembali norepinefrin pada ujung-ujung saraf. Mode aksi dari obat pada saat mengontrol enuresis pada anak diperkirakan terpisah dari efek antidepresannya.

Potensiasi efek dari serotonin dan norepinefrin, selain itu imipramin juga memiliki efek antikolinergik yang signifikan.

Farmakokinetik: Imipramin diabsorbsi dengan baik di saluran cerna, dan didistribusikan secara luas. Kemungkinan imipramin juga melewati plasenta dan masuk ke dalam kelenjar susu. Imipramin dimetabolisme secara ekstensif oleh hati, kebanyakan pada Metabolism and Excretion: Extensively metabolized by liver, mostly on first pass;some conversion to active compounds. Undergoes enterohepatic recirculation andsecretion into gastric juices.Protein Binding: 89%–95%.T 1/2: 8–16 hr.HydrOXYzine/Imipramine[ ]Contraindicated in: Hypersensitivity; cross sensitivity with other antidepressantsmay occur; angle-closure glaucoma; hypersensitivity to tartrazine or sulfites (in somepreparations); recent MI, known history of QTc prolongation, heart failure.Use Cautiously in: Pre-existing CV disease; seizures or history of seizure disorder;may ↑ risk of suicide attempt/ideation esp. during early treatment or dose adjust-ment. Lactation: Drug present in breast milk; discontinue imipramine or bottle-feed.Pregnancy: Studies inconclusive about fetal risk, although there have been reportsof congentital malformations; benefits should clearly outweigh risk to justify use ofimipramine in pregnancy.Adverse Reactions/Side Effects: (CAPITALS indicate life-threatening; underlinesindicate most frequent.)CNS: Drowsiness,fatigue, agitation, confusion, hallucinations, insomnia. EENT: Blurredvision, dry eyes. CV: ARRHYTHMIAS, hypotension, ECG changes. GI: Constipation, drymouth, nausea, paralytic ileus, weight gain. GU: Urinary retention, decreased libido.Derm: Photosensitivity. Endo: Gynecomastia. Hemat: Blood dyscrasias.Interactions: Potentially fatal reactions when used concurrently with MAOIs; discon-tinue MAOI 2 wk before imipramine. Concurrent use with SSRI antidepressantsshould be avoided (fluoxetine should be stopped 5 wk before starting imipramine).Concurrent use with clonidine may result in hypertensive crisis and should be avoided. Imipramine metabolized in liver by cytochrome P450 2D6 enzyme and its

action may be affected by drugs that compete for metabolism by this enzyme, includ-ing other antidepressants, phenothiazines, carbamazepine, class 1C antiarrhythmics(propafenone, flecainide); when used concurrently, dose reduction of one or the otheror both may be necessary. Concurrent use of other drugs, including cimetidine, quini-dine, amiodarone, and ritonavir, that inhibit activity of the enzyme may result in ↑effects of imipramine. Concurrent use with levodopa may result in delayed/↓ absorp-tion of levodopa or hypertension. Blood levels and effects may be ↓ by rifamycins. ↑CNS depression with other CNS depressants including alcohol, antihistamines, cloni-dine, opioids, and sedatives/hypnotics. Barbiturates may alter blood levels andeffects. Adrenergic and anticholinergic side effects may be ↑ with other agents having these properties. Phenothiazines or hormonal contraceptives ↑ levels and87DRUGSH-MImipramineTIME/ACTION PROFILE (antidepressant effect) Route Onset Peak DurationPO, IM Hours 2–6 wk WeeksDRUGSH-M88may cause toxicity. Cigarette smoking (nicotine) may increase metabolism and altereffects. Drug-Natural: Concomitant use of kava, valerian, or chamomile can increaseCNS depression. ↑ Anticholinergic effects with Jimson weed and scopolia.Dosage: PO (Adults): 25–50 mg three to four times daily (not to exceed 300 mg/day); total daily dose may be given at bedtime.PO (Geriatric Clients): 25 mg at bedtime initially, up to 100 mg/day in divided doses.PO (Children >12 yr): Antidepressant: 25–50 mg/day in divided doses (not to exceed100 mg/day).PO (Children 6–12 yr): Antidepressant: 10–30 mg/day in two divided doses.PO (Children ≥ ≥6 yr): Enuresis: 25 mg once daily 1 hr before bedtime; increase if necessary by 25 mg at weekly intervals to 50 mg in children <12 yr, up to 75 mg inchildren >12 yr.IM (Adults): Up to 100 mg/day in divided doses (not to exceed 300 mg/day).Availability (generic available)Tablets: 10 mg, 25 mg, 50 mg. Canadian: 75 mg. COST: $ Capsules: 75 mg, 100 mg,125 mg, 150 mg. COST: $ Injection: 12.5 mg/mL.● Geriatric Considerations: Elderly susceptible to anticholinergic effects; monitorfor ↑ sedation, hypotensive effects; urinary retention in males with BPH. Baselineand periodic ECG to monitor for PR/QT prolongation.● Pediatric/Adolescent Considerations: Safety not established in children <6 yr;monitor closely face to face for suicidality early in Rx and during dosage adjust-ments. Baseline and periodic ECG. Generally considered second-line therapy toSSRI antidepressants.● Clinical Assessments: Evaluate/monitor mood improvement, suicidality. CV dis-ease: baseline ECG and repeated ECGs. Overweight: monitor weight, BMI, FBS,cholesterol before and during Rx. (See BMI/Metabolic Syndrome, Tools tab.)