Hydromorphone


Thông tin thuốc gốc
Chỉ định và Liều dùng
Oral
Moderate to severe pain
Adult: Opioid-naive patient: As conventional tab: 2-4 mg 4-6 hrly as needed. As liq: 2.5-10 mg 3-6 hrly as needed. Dose may be increased gradually if analgesia is inadequate, pain severity increases, or as tolerance develops. Opioid-tolerant patient: As conventional preparation: Dose is adjusted according to prior opioid daily dose to achieve at least 3-4 hr of analgesia. As extended-release tab: Initially, dose is titrated according to prior opioid daily dose taken once daily. Maintenance: Dose is titrated w/ increments of 4-8 mg every 3-4 days until adequate analgesia is achieved.
Elderly: Start at the lower end of dosing range.

Parenteral
Moderate to severe pain
Adult: 1-2 mg via IM or SC inj 2-3 hrly as necessary. Alternatively, 0.2-1 mg 2-3 hrly via slow IV inj over at least 2-3 min. Adjust doses according to individual requirements.
Elderly: Start at the lower end of dosing range.

Rectal
Moderate to severe pain
Adult: As supp: 3 mg 6-8 hrly as needed.
Suy thận
Oral:
CrCl (mL/min) Dosage
<30 Extended-release: Initiate w/ 25% of usual starting dose.
≤60 Conventional: Reduce initial dose. Extended-release: Initiate w/ 50% of usual starting dose.

Parenteral:
Initiate w/ 25-50% of usual starting dose.
Suy gan
Oral:
Extended-release: Moderate: Initiate w/ 25% of usual starting dose. Severe: Contraindicated.

Parenteral:
Moderate: Initiate w/ 25-50% of usual starting dose.
Hướng dẫn pha thuốc
Lyophilised powder for inj: Add 25 mL of sterile water for inj in a vial labelled as containing 250 mg to provide a soln containing 10 mg/mL.
Tương kỵ
Y-site admin: Amphotericin B, gallium nitrate, hyaluronidase, minocycline, pantoprazole, phenytoin, sargramostim, thiopental. Syringe: Ampicillin, diazepam, heparin, hyaluronidase, pantoprazole, phenobarbital, phenytoin.
Chống chỉ định
Resp depression w/o resuscitative equipment, raised intracranial pressures, head injury, convulsive disorder, status asthmaticus, paralytic ileus, acute alcoholism. Comatose patients. Severe hepatic impairment (extended-release). Lactation. Concomitant or w/in 14 days of MAOIs use.
Thận trọng
Patient w/ hypotension w/ hypovolaemia, CNS depression, toxic psychoses, delirium tremens, shock, hypothyroidism, prostatic hypertrophy and hyperplasia, severely impaired pulmonary function, adrenocortical insufficiency (e.g. Addison’s Disease), kyphoscoliosis. Patient following GI surgery. Elderly. Moderate renal and hepatic impairment. Pregnancy (may cause neonatal withdrawal syndrome in prolonged use during pregnancy).
Tác dụng không mong muốn
Apnoea, biliary spasm, bradycardia, confusion, constipation, dependence, difficulty w/ micturition, dizziness, drowsiness, dry mouth, dysphoria, euphoria, flushing, hallucinations, headache, hypotension, lightheadedness, miosis, mood changes, muscle rigidity, nausea, oedema, palpitation, postural hypotension, pruritus, rash, sedation, sexual dysfunction, shock, sleep disturbances, sweating, tachycardia, ureteric spasm, urinary retention, urticaria, vertigo, visual disturbances, vomiting.
Potentially Fatal: Resp depression, cardiac arrest, circulatory depression.
IM/IV/Parenteral/PO/Rectal/SC: C (Prolonged use may cause neonatal opioid withdrawal syndrome.)
Thông tin tư vấn bệnh nhân
This drug may cause drowsiness and dizziness, if affected, do not drive or operate machinery.
Chỉ số theo dõi
Monitor relief of pain, resp and mental status, and BP. Monitor for signs of misuse, abuse, and addiction.
Quá liều
Symptoms: Pin-point pupils, resp depression, somnolence progressing to stupor and coma, skeletal muscle flaccidity, and bradycardia; cold and clammy skin, hypotension, apnoea, pulmonary oedema, circulatory collapse. Management: Supportive treatment w/ primary attention to establishment of patent airway and institution of assisted ventilation. Administer IV naloxone 0.4-2 mg,  may be repeated at 2 min interval if no response, for severe overdosage; and 0.2 mg, followed by increments of 0.1 mg every 2 min, for less severe cases. Employ activated charcoal if significant amount has been ingested w/in 1-2 hr provided that the patient has intact gag reflex or secured airway.
Tương tác
Additive depressant effects w/ sedative/hypnotics, general anaesth, antipsychotics (e.g. phenothiazines), tranquilizers, and neuromuscular blockers. Reduced analgesic effect and may precipitate withdrawal symptoms w/ mixed agonist/antagonist opioid analgesics (e.g. pentazocine, nalbuphine, butorphanol, buprenorphine).
Potentially Fatal: CNS excitation or depression may occur when given w/ MAOIs.
Tương tác với thức ăn
Additive CNS depression w/ alcohol. Increased peak plasma concentration resulting in potentially toxic doses of hydromorphone (extended-release) when taken w/ alcohol.
Tác dụng
Description:
Mechanism of Action: Hydromorphone, a phenanthrene derivative, is an opiate agonist w/ greater analgesic potency than morphine. It binds to µ-opioid receptors in the CNS and smooth muscles, causing inhibition of ascending pain pathways, altering perception of and response to pain, and producing generalised CNS depression. Additionally, it may directly supress the resp reflex, thereby causing resp depression.
Onset: 15-30 min (conventional preparations); 6 hr (extended-release preparations); 5 min (IV).
Duration: 3-4 hr (conventional preparations, IV); approx 13 hr (extended-release preparations).
Pharmacokinetics:
Absorption: Rapidly but incompletely absorbed from the GI tract. Time to peak plasma concentration: ≤1 hr (conventional); 12-16 hr (extended-release). Bioavailability: Approx 24%.
Distribution: Widely distributed in the tissues; crosses the placenta and enters breast milk. Volume of distribution: 4 L/kg. Plasma protein binding: Approx 8-19%.
Metabolism: Extensively metabolised in the liver via glucuronidation to inactive metabolites (>95% as hydromorphone-3-glucuronide, minor amounts as 6-hydroxy reduction metabolites); undergoes extensive first-pass metabolism.
Excretion: Via urine (mainly as glucuronide conjugates). Terminal elimination half-life: 2.3 hr (conventional); 8-15 hr (extended-release).
Đặc tính

Chemical Structure Image
Hydromorphone

Source: National Center for Biotechnology Information. PubChem Database. Hydromorphone, CID=5284570, https://pubchem.ncbi.nlm.nih.gov/compound/Hydromorphone (accessed on Jan. 23, 2020)

Bảo quản
Store between 15-30°C. Protect from light.
Phân loại MIMS
Thuốc giảm đau (opioid)
Phân loại ATC
N02AA03 - hydromorphone ; Belongs to the class of natural opium alkaloids. Used to relieve pain.
Tài liệu tham khảo
Anon. Hydromorphone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/06/2016.

Buckingham R (ed). Hydromorphone Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/06/2016.

Dilaudid Injection; Dilaudid-HP Injection (Purdue Pharma LP). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 18/01/2017.

Dilaudid Tablet (Cardinal Health). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 18/01/2017.

Exalgo Tablet, Extended Release (Mallinckrodt, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 18/01/2017.

Joint Formulary Committee. Hydromorphone Hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/06/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Hydromorphone Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 08/06/2016.

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