Atropa Belladonna And Opium

FDA Drug Information • Also known as: Belladonna And Opium

Brand Names: Belladonna And Opium
Route: RECTAL
Dosage Form: SUPPOSITORY
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: ADDICTION, ABOUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; NEONATAL OPIOD WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH ALCOHOL, BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Belladonna and opium suppositories expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing belladonna and opium suppositories, and monitor all patients regularly for the development of these behaviors or conditions [ see Warnings and Precautions (5.1) ]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of belladonna and opium suppositories. Monitor for respiratory depression, especially during initiation of belladonna and opium suppositories or following a dose increase [ see Warnings and Precautions (5.2) ]. Accidental Exposure Accidental exposure of even one dose of belladonna and opium suppositories, especially by children, can result in a fatal overdose of opium [ see Warnings and Precautions (5.2) ]. Neonatal Opioid Withdrawal Syndrome Prolonged use of belladonna and opium suppositories during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [ see Warnings and Precautions (5.3) ]. Risks From Concomitant Use With Alcohol, Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [ see Warnings and Precautions (5.4), Drug Interactions (7) ].

Reserve concomitant prescribing of belladonna and opium suppositories and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.

Limit dosages and durations to the minimum required.

Follow patients for signs and symptoms of respiratory depression and sedation WARNING: ADDICTION, ABOUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; NEONATAL OPIOD WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH ALCOHOL, BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning.

Belladonna and opium suppositories expose users to risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and monitor regularly for these behaviors or conditions. (5.1)

Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. (5.2)

Accidental exposure of belladonna and opium suppositories, especially by children, can result in a fatal overdose of opium. (5.2)

Prolonged use of belladonna and opium suppositories during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. (5.3)

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. (5.4, 7)

Description

11 DESCRIPTION Each belladonna and opium suppository contains (in a water-soluble base consisting of polyethylene glycol 400, 1450, 8000 and polysorbate 60): Belladonna (16.2 mg) and Opium (30 mg): Powdered belladonna extract 16.2 mg and powdered opium 30 mg (Warning: May be habit forming). Belladonna (16.2 mg) and Opium (60 mg): Powdered belladonna extract 16.2 mg and powdered opium 60 mg (Warning: May be habit forming). This drug falls into the pharmacological/therapeutic class of narcotic analgesic/antispasmotic agents. The pharmacologically active principles present in the belladonna extract component of belladonna and opium suppositories are: Established Name: Atropine Chemical Name: dl Tropyl Tropate Established Name: Scopolamine Chemical Name: dl Scopolamine Opium contains more than twenty alkaloids, the principle ones being morphine (10%), narcotine (6%), papaverine (1%) and codeine (0.5%). The major pharmacologically active principle of the powdered opium component of belladonna and opium suppositories, however, is: Name: Morphine Chemical Name: 7, 8-Didehydro-4, 5-epoxy-17-Methyl-morphinan-3, 6-diol

What Is Atropa Belladonna And Opium Used For?

1 INDICATIONS AND USAGE Belladonna and opium suppositories are indicated for the management of ureteral spasm pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [ see Warnings and Precautions (5.1) ], reserve belladonna and opium suppositories for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:

Have not been tolerated, or are not expected to be tolerated,

Have not provided adequate analgesia, or are not expected to provide adequate analgesic Belladonna and opium suppositories are an opioid agonist indicated for the management of ureteral spasm pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see Warnings and Precautions (5.1)], reserve belladonna and opium suppositories for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:

Have not been tolerated, or are not expected to be tolerated,

Have not provided adequate analgesia, or are not expected to provide adequate analgesia

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. (2.1)

Individualize dosing based on the severity of pain, patient response, and prior analgesic experience, and risk factor for addiction, abuse, and misuse. (2.1)

Initiate dosing with one suppository once or twice daily as needed for pain. (2.2)

Do not stop belladonna and opium suppositories abruptly in a physically dependent patient. (2.4) 2.1 Important Dosage and Administration Instructions Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [ see Warnings and Precautions (5) ]. Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [ see Warnings and Precautions (5.1) ]. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with belladonna and opium suppositories and adjust the dosage accordingly [ see Warnings and Precautions (5.2) ]. 2.2 Dosing One belladonna and opium suppository rectally once or twice daily, not to exceed four doses daily or as recommended by the physician. Moisten finger and suppository with water before inserting. Absorption is dependent on body hydration and not on body temperature. Not recommended for use in children 12 years of age and under. Conversion from Other Opioids to Belladonna and Opium Suppositories There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of belladonna and opium suppositories. It is safer to underestimate a patient’s 24-hour belladonna and opium suppositories dosage than to overestimate the 24-hour belladonna and opium suppositories dosage and manage an adverse reaction due to overdose. Conversion from Belladonna and Opium suppositories to Extended-Release Opioid The relative bioavailability of belladonna and opium suppositories compared to extended-release opioid is unknown, so conversion to extended-release drug product must be accompanied by close observation for signs of excessive sedation and respiratory depression. 2.3 Maintenance of Therapy Continually reevaluate patients receiving belladonna and opium suppositories to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [ see Warnings and Precautions (5.1) ]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. If the level of pain increases after dosage stabilization, attempt to identify the source of...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Belladonna may cause drowsiness, dry mouth, urinary retention, photophobia, rapid pulse, dizziness and blurred vision 7 . Opium usage may result in constipation, nausea or vomiting. Pruritis and urticaria may occasionally occur. Hypersensitivity to opium or belladonna may occur. The following serious adverse reactions are described, or described in greater detail, in other sections:

Addiction, Abuse, and Misuse [ see Warnings and Precautions (5.1) ]

Life-Threatening Respiratory Depression [ see Warnings and Precautions (5.2) ]

Neonatal Opioid Withdrawal Syndrome [ see Warnings and Precautions (5.3) ]

Interactions with Benzodiazepines and Other CNS Depressants [ see Warnings and Precautions (5.4) ]

Adrenal Insufficiency [ see Warnings and Precautions (5.6) ]

Severe Hypotension [ see Warnings and Precautions (5.7) ]

Gastrointestinal Adverse Reactions [ see Warnings and Precautions (5.9) ]

Seizures [ see Warnings and Precautions (5.11) ]

Withdrawal [ see Warnings and Precautions (5.12) ] Most common adverse reactions are drowsiness, dry mouth, urinary retention, photophobia, rapid pulse, dizziness and blurred vision, constipation, nausea and vomiting. (6) To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of opioids. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis: Anaphylaxis has been reported with products containing opioids. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids

Drug Interactions

7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with belladonna and opium suppositories. Table 1: Clinically Significant Drug Interactions with Belladonna and Opium Suppositories Alcohol, Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact : Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention : Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [ see Warnings and Precautions (5.4) ]. Examples : Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol. Serotonergic Drugs Clinical Impact : The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention : If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue belladonna and opium suppositories if serotonin syndrome is suspected. Examples : Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAOI) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact : MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [ see Warnings and Precautions (5.2) ] If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. Intervention : The use of belladonna and opium suppositories is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Examples : phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact : May reduce the analgesic effect of belladonna and opium suppositories and/or precipitate withdrawal symptoms. Intervention : Avoid concomitant use. Examples : butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact : Opium may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention : Monitor patients for signs of respiratory depression that may be...

Contraindications

4 CONTRAINDICATIONS

Belladonna and opium suppositories are contraindicated in patients with:

Significant respiratory depression [ see Warnings and Precautions (5.2) ]

Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [ see Warnings and Precautions (5.5) ]

Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [ see Warnings and Precautions (5.7), Drug Interactions (7) ]

Known or suspected gastrointestinal obstruction, including paralytic ileus [ see Warnings and Precautions (5.9) ]

Hypersensitivity to opium or belladonna [ see Adverse Events (6) ]

Glaucoma 2

Severe hepatic or renal disease 2

Narcotic idiosyncrasies 2

Convulsive disorders 2

Acute alcoholism 2

Delirium tremens 2

Premature labor 2

Significant respiratory depression. (4)

Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. (4)

Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (4)

Known or suspected gastrointestinal obstruction, including paralytic ileus. (4)

Hypersensitivity to opium or belladonna. (4)

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. There are no available data with belladonna and opium suppositories in pregnant women to inform a drug associated risk for major birth defects and miscarriage. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [ see Warnings and Precautions (5.3) ]. Belladonna refers to plant alkaloids that contain anticholinergic agents such as atropine. Atropine used in human pregnancies has not been associated with birth defects or adverse fetal effects although the drug readily crosses the placenta. Use during pregnancy may increase risk of respiratory abnormalities, hypospadias, and eye or ear malformations but causal relationship is unclear. The Collaborative Perinatal Project found no relationship between first trimester use of atropine and birth defects in the offspring but found an increase in birth defects in general in the offspring of pregnancies where the mother had taken belladonna. There was no relationship to any particular syndrome of anomalies. A statistically significant (although weak) association was discovered between congenital anomalies and maternal use of belladonna. A study was conducted based on the infants of 554 women who took belladonna during the...

Overdosage

10 OVERDOSAGE Clinical Presentation Acute overdose with belladonna and opium suppositories can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [ see Clinical Pharmacology (12) ]. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to opium overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to opium overdose. Because the duration of opioid reversal is expected to be less than the duration of action of opium in belladonna and opium suppositories, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Belladonna (16.2 mg) and Opium (30 mg) suppositories are brown, bullet shaped suppositories. NDC 63629-8436-1: Carton of 4 suppositories Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. DO NOT REFRIGERATE. PROTECT FROM MOISTURE DURING STORAGE. Rx Only

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.