Class: Opiate Agonists
VA Class: CN101
CAS Number: 8002-76-4
Brands: B & O

Introduction

Opiate agonist and antiperistaltic agent; naturally occurring phenanthrene derivative; contains several alkaloids, including anhydrous morphine, codeine, and papaverine.a b c d g h

Uses for Opium

Pain Associated with Ureteral Spasm

Used rectally in combination with belladonna extract for the relief of moderate to severe pain associated with ureteral spasm unresponsive to nonopiate analgesics.a d

Used when the analgesic, sedative, and antispasmodic effects of the combination may be useful (i.e., when pain and smooth-muscle spasm are present concurrently)a and to space intervals between opiate injections.d

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Diarrhea

Paregoric or opium tincture are used principally for the treatment of diarrhea.a b g h

Should not be used for treatment of diarrhea caused by poisoning until the toxic material is eliminated from the GI tract by gastric lavage or cathartics.b g h (See Contraindications.)

Opiate Withdrawal

Used as a tincture (e.g., paregoric or diluted opium tincture) to treat opiate withdrawal symptoms (e.g., generalized tremors, hypertonicity with any form of tactile stimuli, hyperalertness, sleeplessness, excessive crying, vomiting, diarrhea, yawning, fever) in neonates born to women addicted to opiates.a b c

Diluted opium tincture is preferred by some clinicians to paregoric tincture for the treatment of opiate withdrawal symptoms in neonates, since paregoric contains camphor and benzoic acid which may cause potential adverse effects.b

Opium Dosage and Administration

Administration

Administer orally as a solution.b g h

Administer rectally as a suppository.a d

Oral Administration

Paregoric and opium tincture are administered orally as a solution.b g h

Opium tincture contains 25 times more morphine than does paregoric and should never be confused with the latter preparation.b f (See Concentrated Opium Solutions and also Possible Prescribing and Dispensing Errors, under Cautions.)

Dilution

For treatment of opiate withdrawal symptoms in neonates, opium tincture must be diluted and administered as a 1:25 dilution in water.b

Rectal Administration

Opium is administered rectally as a suppository in combination with belladonna extract.a d

Moisten finger and rectal suppository containing belladonna and opium with water prior to rectal insertion.a d

Dosage

Tincture: Available as opium and paregoric; dosage is expressed in terms of anhydrous morphine alkaloid.b f g h i

Opium tincture is an alcoholic solution containing 50 mg of anhydrous morphine (as granulated or sliced opium) per 5 mL.b h

Paregoric contains 2 mg of anhydrous morphine (usually as opium), anise oil, benzoic acid, glycerin, and sufficient diluted alcohol to make 5 mL.b g

Rectal suppository: Available as a fixed combination containing opium and belladonna; dosage expressed in terms of opium and belladonna.d

Should be given in the smallest effective dose and as infrequently as possible to minimize the development of tolerance and physical dependence.a c h

Pediatric Patients

Diarrhea
Paregoric
Oral

Usually, 0.25–0.5 mL/kg 1–4 times daily.b g

Opiate Withdrawal
Paregoric or 1:25 Dilution of Opium Tincture
Oral

To prevent potential overdose, opium tincture must be diluted and administered as a 1:25 dilution in water.b (See Concentrated Opium Solutions and also Possible Prescribing and Dispensing Errors, under Cautions.)

Neonates: Usually, 3–6 drops every 3–6 hours as needed; adjust dosage to control withdrawal symptoms.b Alternatively, initially, 0.2 mL every 3 hours and increase, if necessary, by approximately 0.05 mL every 3 hours until withdrawal symptoms are controlled; rarely necessary to exceed 0.7 mL per dose.b After withdrawal symptoms have stabilized for 3–5 days, gradually decrease dosage over a 2- to 4-week period.b c

Adults

Pain Associated with Ureteral Spasm
Opium Combination Suppository
Rectal

Usually, 1 suppository once or twice daily, or as directed by a clinician.a d

Diarrhea
Paregoric
Oral

Usually, 5–10 mL 1–4 times daily.b g

Opium Tincture
Oral

Opium tincture contains 25 times more morphine than does paregoric and should never be confused with the latter preparation.b f (See Concentrated Opium Solutions and also Possible Prescribing and Dispensing Errors, under Cautions.)

Usually, 0.6 mL 4 times daily;b h may range from 0.3–1 mL 4 times daily.b

Prescribing Limits

Pediatric Patients

Opiate Withdrawal
Paregoric or 1:25 Dilution of Opium Tincture
Oral

Neonates: Rarely necessary to exceed 0.7 mL per dose.b

Adults

Pain Associated with Ureteral Spasm
Opium Combination Suppository
Rectal

Maximum 1 suppository 4 times daily.d

Diarrhea
Opium Tincture
Oral

Maximum 1 mL as a single dose or 6 mL daily.b

Special Populations

Hepatic Impairment

Use with caution and reduce initial dosage in patients with hepatic cirrhosis or insufficiency.b c g h

Renal Impairment

Use with caution and reduce initial dosage in patients with renal impairment.c g

Geriatric and Debilitated Patients

Administer with caution and reduce dosage in geriatric or debilitated patients.b c d g h

Cautions for Opium

Contraindications

  • Known hypersensitivity to opium or morphine.c g

  • Convulsive states (e.g., status epilepticus, tetanus, strychnine poisoning).d g

  • Undiluted opium tincture: Children.h (See Pediatric Use under Cautions.)

  • Paregoric and opium tincture: Diarrhea caused by poisoning until the toxic material is eliminated from the GI tract.g h

  • Opium and belladonna combination suppository: Glaucoma, severe renal or hepatic disease, bronchial asthma, respiratory depression, acute alcoholism, delirium tremens, premature labor.d

Warnings/Precautions

Warnings

Dependence and Abuse

Abuse potential exists; use with caution.d g h

Does not produce analgesia or euphoria in usual oral antidiarrheal doses; therefore, opium preparations may be used in the treatment of acute diarrhea with little risk of development of physical dependence in the patient.b However, prolonged use of opium preparations (e.g., patients with ileitis or colitis) may produce physical dependence.b g

Use with caution in patients with a history of opiate agonist dependence.b

Mild withdrawal symptoms reported in patients receiving paregoric 10 mg every 4 hours for 1–2 weeks.g Provide supportive care in a hospital setting for patients in opiate withdrawal.g

Concentrated Opium Solutions

Serious adverse events and deaths have occurred when opium tincture was mistakenly interchanged for paregoric (also known as “camphorated tincture of opium” and “tincture of paregoric”).f These medication errors resulted in fatal adverse events because opium tincture is 25 times more concentrated than paregoric.f FDA recommends a poison label for all containers of opium tincture stating the strength of morphine per mL and a statement such as “WARNING! Do NOT confuse opium tincture with paregoric.”f

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription spelling; similarity in acronyms for diluted tincture of opium and deodorized tincture of opium (e.g., DTO), which contains 25 times more opium.e May result in fatal errors.e

It is important that prescriptions for opium preparations be written clearly and filled with the proper concentration to prevent potential medication errors.e

General Precautions

Head Injury and Increased Intracranial Pressure

Respiratory depressant effects (with CO2 retention and secondary elevation of CSF pressure) may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a preexisting increase in intracranial pressure.g h

May produce effects that obscure the clinical course in patients with head injuries.g

Use with extreme caution, if at all, in patients with a head injury, brain tumor, or elevated CSF pressure.c

Hypotensive Effects

Like all opiate analgesics, may cause severe hypotension in the postoperative patient or any individual whose ability to maintain their BP is compromised by a depleted blood volume or concomitant drugs (e.g., phenothiazines, general anesthetics).c g

May produce orthostatic hypotension in ambulatory patients.c Lightheadedness and dizziness appear to be more prominent in ambulatory patients; may be alleviated if the patient lies down.g

Respiratory Effects

Respiratory depression requiring administration of naloxone or ventilatory support may result from toxic dosages.d g

May decrease respiratory drive to the point of apnea while simultaneously increasing airway resistance, even at usual therapeutic doses.g Use with extreme caution in patients with disorders characterized by hypoxia.g

Use with caution in patients with asthma or emphysema.b c

Acute Abdominal Conditions

Administration may complicate assessment of patients with acute abdominal conditions.g

Reduce the initial dosage in patients who have undergone GI surgery.c Use with caution in patients with GI hemorrhage.h

CNS Effects

May impair mental and/or physical abilities needed to perform potentially hazardous activities such as driving or operating machinery.c g Individuals who perform hazardous tasks requiring mental alertness or physical coordination should be warned about possible adverse CNS effects of opiate agonists.c g

May aggravate preexisting seizures in patients with convulsive disorders.c g Risk of seizures in patients without a history of seizure disorders at dosages above recommended levels.g

Prostatic Hypertrophy or Urethral Stricture

Use with caution in patients with severe prostatic hypertrophy or urethral stricture.b d g

Hypothyroidism and Myxedema

Use with caution and reduce the initial dosage in patients with hypothyroidism.c g

Use with caution in patients with untreated myxedema.c h

Addison’s Disease

Use with caution and reduce the initial dosage in patients with Addison’s disease.c g

Cardiac Arrhythmia

May increase ventricular response rate through a vagolytic action; use with caution in patients with atrial flutter or other supraventricular tachycardias.c g

Cerebral Arteriosclerosis.

Use with caution in patients with cerebral arteriosclerosis.h

Fixed-Combination Preparations

Consider the cautions, precautions, and contraindications associated with other drug(s) in fixed-combination preparations.a d h

Specific Populations

Pregnancy

Category C.d g h

Lactation

Morphine is distributed into milk.g Use with caution in nursing women.d g h

Pediatric Use

Manufacturer does not recommend use of opium rectal suppositories in children ≤12 years of age.d

Manufacturer does not recommend use of opium tincture in children;h however, diluted opium tincture has been used to treat opiate withdrawal symptoms in neonates born to women addicted to opiates.a c

Geriatric Use

Use with caution in geriatric patients.d g

Hepatic Impairment

Use with caution in patients with severe hepatic impairment.d g

Renal Impairment

Use with caution in patients with severe renal impairment.d g

Common Adverse Effects

Opium tincture and fixed-combination suppositories: Constipation,d h nausea,d h vomiting.d h

Paregoric: Lightheadedness,g dizziness,g sedation,g nausea,g vomiting.g

Interactions for Opium

Specific Drugs

Drug

Interaction

Comments

CNS depressants (other opiates, general anesthetics, tranquilizers, sedatives, hypnotics, alcohol)

May potentiate the effects of other CNS depressantsc g

Use concomitantly with great caution and in reduced dosagea c g h

Some tranquilizers, especially phenothiazines, may antagonize opiate agonist analgesiac

Diuretics

Opiate agonists may decrease the effects of diuretics in patients with CHFc

Opiate partial agonists (butorphanol, nalbuphine, pentazocine)

Possible reduced analgesic effect and/or withdrawal symptoms

Avoid concomitant use

Skeletal muscle relaxants

May enhance the neuromuscular blocking action of skeletal muscle relaxantsc

Opium Pharmacokinetics

Absorption

Bioavailability

Following oral administration, morphine is variably absorbed from the GI tract.a b h

Onset

Following rectal administration, analgesia occurs in 15–30 minutes.a

Duration

Following rectal administration, analgesia is maintained for 3–5 hours.a

Elimination

Metabolism

Metabolized principally in the liver and undergoes conjugation with glucuronic acid.a b c h

Secondary conjugation may also occur to form 3,6-diglucuronide.a b h

Elimination Route

Excreted principally in urine as metabolites and to a lesser extent as unchanged drug.a b h

Approximately 75% of morphine excreted in the urine within 48 hours.a b h

Stability

Storage

Oral

Solution

Paregoric: Tight, light-resistant containers at 15–30°C.b g A sediment may form if exposed to low temperatures; filter if necessary.g Avoid exposure to direct sunlight and to excessive heat.b

Opium tincture: Tight, light-resistant containers at 15–30° C.b h Avoid exposure to direct sunlight and to excessive heat.b

Rectal

Suppositories

Room temperature.d Do not refrigerate.d Protect from moisture.d

Actions

  • Analgesic activity results primarily from the morphine content of opium preparations.a d h

  • Increases smooth muscle tone in the longitudinal muscle of the GI tract, inhibits GI motility and propulsive contraction, and diminishes digestive secretions.b h

  • Relatively small doses of opium are effective in controlling diarrhea, but do not produce substantial analgesia.a b h

  • Papaverine content of the mixed alkaloids is too small to have demonstrable smooth muscle relaxant activity.a b h

Advice to Patients

  • Importance of informing patients that drug may impair mental and/or physical ability required for performance of potentially hazardous tasks.c g

  • Importance of informing patients that opium preparations should not be combined with alcohol or other CNS depressants (e.g., sleep medications, tranquilizers).g h

  • Importance of informing patients that this is a drug of potential abuse.d g h

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.g

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.g h

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Opium preparations are subject to control under the Federal Controlled Substances Act of 1970 as schedule II (C-II) drugs, but as schedule III (C-III) drugs when they contain ≤25 mg of opium per 5 mL, 5 g, or dosage unit in fixed combination with a therapeutic amount of one or more nonopiate drugs or as schedule V (C-V) drugs when they contain 1 mg or less of opium per mL or g in combination with one or more active nonopiate medicinal ingredients in sufficient proportion to confer on the preparation medicinal qualities not possessed by opium.a b

Powdered Opium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Powdered Opium Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Rectal

Suppositories

30 mg with Belladonna Extract 16.2 mg (equivalent to belladonna alkaloids 0.21 mg)*

B&O Supprettes No. 15A (C-II)

Amerifit

60 mg with Belladonna Extract 16.2 mg (equivalent to belladonna alkaloids 0.21 mg)*

B&O Supprettes No. 16A (C-II)

Amerifit

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Opium Tincture (Deodorized Opium Tincture, Laudanum)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tincture

50 mg (of morphine anhydrous) per 5 mL*

Opium Tincture Deodorized (C-II)

Marathon

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Paregoric (Camphorated Opium Tincture)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tincture*

2 mg (of morphine anhydrous) per 5 mL*

Paregoric (C-III)

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions May 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

a. AHFS Drug Information 2007. McEvoy GK, ed. Opium. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2152.

b. AHFS Drug Information 2007. McEvoy GK, ed. Opium Preparations. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2917-8.

c. AHFS Drug Information 2007. McEvoy GK, ed. Opiate Agonists General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2123-28.

d. Paddock Laboratories. Belladonna & opium rectal suppositories prescribing information. Minneapolis, MN; Undated.

e. Food and Drug Administration. Drug Errors Caused by Abbreviations. FDA Patient Safety News: Show #15. FDA Patient Safety News May 2003. From FDA web site .

f. Food and Drug Administration. Dangerous Mixups Between Opium Tincture and Paregoric. FDA Patient Safety News: Show #27, May 2004. From FDA web site.

g. Actavis. Paregoric (camphorated opium tincture) [Morphine anhydrous (opium 2 mg)] prescribing information. Baltimore, MD; 2006 Feb.

h. Ranbaxy. Opium tincture (deodorized) prescribing information. Jacksonville, FL; 2004 Dec.

i. Code of federal regulations. Part 1304.31. Reports from manufacturers importing narcotic raw material. Revised as of April 1, 2006.

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