B & O

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

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

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

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

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.j Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.j

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.j If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.j In some patients, switching to a different opiate improved symptoms.j

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

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;j k l m n causality not established.j Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.j Perform appropriate laboratory testing in patients with manifestations of hypogonadism.j

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

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

• 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

• Potential risk of serotonin syndrome with concurrent use of opiates and other serotonergic agents.j Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia, labile BP, fever, excessive sweating, shivering, shaking, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea) develop.j

• Potential risk of adrenal insufficiency.j Importance of contacting clinician if manifestations of adrenal insufficiency (e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, hypotension) develop.j

• Possible risk (although causality not established) of hypogonadism or androgen deficiency with long-term opiate agonist or partial agonist use.j Importance of informing clinician if decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility occurs.j

• 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.)