gic 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 greater than otherwise expected and decrease the dosage of belladonna and opium suppositories and/or the muscle relaxant as necessary. diuretics clinical impact : opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. intervention : monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. anticholinergic drugs clinical impact : the concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. intervention : monitor patients for signs of urinary retention or reduced gastric motility when belladonna and opium suppositories are used concomitantly with anticholinergic drugs. • serotonergic drugs: concomitant use may result in serotonin syndrome. discontinue belladonna and opium suppositories if serotonin syndrome is suspected. (7) • monoamine oxidase inhibitors (maois): can potentiate the effects of opium. avoid concomitant use in patients receiving maois or within 14 days of stopping treatment with an maoi. (7) • mixed agonist/antagonist and partial agonist opioid analgesics: avoid use with belladonna and opium suppositories because they may reduce analgesic effect of belladonna and opium suppositories or precipitate withdrawal symptoms. (7)

ended 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

opioid, belladonna and opium suppositories exposes users to the risks of addiction, abuse, and misuse [ see drug abuse and dependence (9) ]. although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed belladonna and opium suppositories. addiction can occur at recommended dosages and if the drug is misused or abused. assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing belladonna and opium suppositories, and monitor all patients receiving belladonna and opium suppositories for the development of these behaviors or conditions. risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). the potential for these risks should not, however, prevent the proper management of pain in any given patient. patients at increased risk may be prescribed opioids such as belladonna and opium suppositories, but use in such patients necessitates intensive counseling about the risks and proper use of belladonna and opium suppositories along with intensive monitoring for signs of addiction, abuse, and misuse. opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. consider these risks when prescribing or dispensing belladonna and opium suppositories. strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [ see patient counseling information (17) ]. contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.2 life-threatening respiratory depression serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [ see overdosage (10) ]. carbon dioxide (co 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. while serious, life-threatening, or fatal respiratory depression can occur at any time during the use of belladonna and opium suppositories, the risk is greatest during the initiation of therapy or following a dosage increase. monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of belladonna and opium suppositories. to reduce the risk of respiratory depression, proper dosing of belladonna and opium suppositories is essential [ see dosage and administration (2.2) ]. overestimating the belladonna and opium suppositories dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. accidental exposure of even one dose of belladonna and opium suppositories, especially by children, can result in respiratory depression and death due to an overdose of opium. 5.3 neonatal opioid withdrawal syndrome prolonged use of belladonna and opium suppositories during pregnancy can result in withdrawal in the neonate. neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, 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 use in specific populations (8.1), patient counseling information ]. 5.4 risks from concomitant use with alcohol, benzodiazepines or other central nervous system depressants profound sedation, respiratory depression, coma, and death may result from the concomitant use of belladonna and opium suppositories with benzodiazepines or other cns depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other cns depressant drugs with opioid analgesics [ see drug interactions (7) ]. if the decision is made to prescribe a benzodiazepine or other cns depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. in patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other cns depressant than indicated in the absence of an opioid, and titrate based on clinical response. if an opioid analgesic is initiated in a patient already taking a benzodiazepine or other cns depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. follow patients closely for signs and symptoms of respiratory depression and sedation. advise both patients and caregivers about the risks of respiratory depression and sedation when belladonna and opium suppositories are used with benzodiazepines or other cns depressants (including alcohol and illicit drugs). advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other cns depressant have been determined. screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional cns depressants including alcohol and illicit drugs [ see drug interactions (7) and patient counseling information (17) ]. 5.5 life-threatening respiratory depression in patients with chronic pulmonary disease or in elderly, cachectic, or debilitated patients the use of belladonna and opium suppositories in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated. patients with chronic pulmonary disease : belladonna and opium suppositories-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of belladonna and opium suppositories [ see warnings and precautions (5.2) ]. elderly, cachetic, or debilitated patients : life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [ see warnings and precautions (5.2) ]. monitor such patients closely, particularly when initiating and titrating belladonna and opium suppositories and when belladonna and opium suppositories is given concomitantly with other drugs that depress respiration [ see warnings and precautions (5.2) ]. alternatively, consider the use of non-opioid analgesics in these patients. 5.6 interactions with monoamine oxidase inhibitors monoamine oxidase inhibitors (maois) may potentiate the effects of opioids, including respiratory depression, coma, and confusion. belladonna and opium suppositories should not be used in patients taking maois or within 14 days of stopping such treatment. 5.7 adrenal insufficiency cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. if adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. the information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. 5.8 severe hypotension belladonna and opium suppositories may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain cns depressant drugs (e.g., phenothiazines or general anesthetics) [ see drug interactions (7) ]. monitor these patients for signs of hypotension after initiating or titrating the dosage of belladonna and opium suppositories. in patients with circulatory shock, belladonna and opium suppositories may cause vasodilation that can further reduce cardiac output and blood pressure. avoid the use of belladonna and opium suppositories in patients with circulatory shock. 5.9 risks of use in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness in patients who may be susceptible to the intracranial effects of co 2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), belladonna and opium suppositories may reduce respiratory drive, and the resultant co 2 retention can further increase intracranial pressure. monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with belladonna and opium suppositories. opioids may also obscure the clinical course in a patient with a head injury. avoid the use of belladonna and opium suppositories in patients with impaired consciousness or coma. 5.10 risks of use in patients with gastrointestinal conditions belladonna and opium suppositories are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. the opium in belladonna and opium suppositories may cause spasm of the sphincter of oddi. opioids may cause increases in serum amylase. monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. 5.11 increased risk of seizures in patients with seizure disorders the opium in belladonna and opium suppositories may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. monitor patients with a history of seizure disorders for worsened seizure control during belladonna and opium suppositories therapy. 5.12 withdrawal avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including belladonna and opium suppositories. in these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [ see drug interactions (7) ]. when discontinuing belladonna and opium suppositories, gradually taper the dosage [ see dosage and administration (2.4) ]. do not abruptly discontinue belladonna and opium suppositories [ see drug abuse and dependence (9.3) ]. 5.13 risks of driving and operating machinery belladonna and opium suppositories may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of belladonna and opium suppositories and know how they will react to the medication [see patient counseling information (17)].

iratory 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 increased pain before increasing the belladonna and opium suppositories dosage. if unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. 2.4 discontinuation of belladonna and opium suppositories when a patient who has been taking belladonna and opium suppositories regularly and may be physically dependent no longer requires therapy with belladonna and opium suppositories, use a gradual downward titration of the dosage to prevent signs and symptoms of withdrawal. do not stop belladonna and opium suppositories abruptly [ see warnings and precautions (5.12), drug abuse and dependence (9.3) ].

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

gic 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 greater than otherwise expected and decrease the dosage of belladonna and opium suppositories and/or the muscle relaxant as necessary. diuretics clinical impact : opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. intervention : monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. anticholinergic drugs clinical impact : the concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. intervention : monitor patients for signs of urinary retention or reduced gastric motility when belladonna and opium suppositories are used concomitantly with anticholinergic drugs. • serotonergic drugs: concomitant use may result in serotonin syndrome. discontinue belladonna and opium suppositories if serotonin syndrome is suspected. (7) • monoamine oxidase inhibitors (maois): can potentiate the effects of opium. avoid concomitant use in patients receiving maois or within 14 days of stopping treatment with an maoi. (7) • mixed agonist/antagonist and partial agonist opioid analgesics: avoid use with belladonna and opium suppositories because they may reduce analgesic effect of belladonna and opium suppositories or precipitate withdrawal symptoms. (7)

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 first four months of pregnancy. the study was conducted in the collaborative perinatal project and showed that belladonna is unlikely to cause minor congenital abnormalities. the estimated maximum risk is most likely less than 3% if maternal belladonna is used early in pregnancy. 1 labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. belladonna and opium suppositories is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including belladonna and opium suppositories, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. 8.2 lactation risk summary the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for belladonna and opium suppositories and any potential adverse effects on the breastfed infant from belladonna and opium suppositories or from the underlying maternal condition. clinical considerations infants exposed to belladonna and opium suppositories through breast milk should be monitored for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. 8.3 females and males of reproductive potential infertility chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.1)]. 8.4 pediatric use the safety and effectiveness of belladonna and opium suppositories in pediatric patients have not been established. 8.5 geriatric use elderly patients (aged 65 years or older) may have increased sensitivity to belladonna and opium. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of belladonna and opium suppositories slowly in geriatric patients [ see warnings and precautions (5.2) ].

yndrome 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 first four months of pregnancy. the study was conducted in the collaborative perinatal project and showed that belladonna is unlikely to cause minor congenital abnormalities. the estimated maximum risk is most likely less than 3% if maternal belladonna is used early in pregnancy. 1 labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. belladonna and opium suppositories is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including belladonna and opium suppositories, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

process. additionally, the side effect of euphoria may contribute to sense of pain relief. 12.2 pharmacodynamics through its parasympatholytic action, atropine (belladonna) relaxes smooth muscle resulting from parasympathetic stimulation. it is the dl isomer of l-hyoscyamine and therefore exhibits the same clinical effects. it is, however, approximately one-half as active peripherally as l-hyoscyamine, the latter being the major active plant alkaloid. the dl isomer atropine is formed during the process of isolation of the belladonna extract. 1 morphine, the major active principle of powdered opium, is responsible for the action of powdered opium although the other alkaloids present also contribute to it. the sedative and analgesic action of morphine, the effect desired by inclusion in belladonna and opium suppositories of powdered opium, are thought to be due to the depressant effect on the cerebral cortex, hypothalamus and medullary centers. in large doses, the opiates and their analogs also exhibit synaptic conduction in the spinothalamic tracts, depress the function of the reticular formation, the lemniscus and the thalamic relays, and inhibit spinal synaptic reflexes: but these inhibitor actions should not be elicited with therapeutic doses of the drug. moderate doses of powdered opium should not alter the electroencephalogram. the action of morphine consists mainly of a descending depression of the central nervous system. it exerts its analgesic action by increasing the pain threshold or the magnitude of stimulus required to evoke pain and by dulling the sensibility or reaction to pain. in addition to its action in abolishing pain, morphine induces a sense of well-being (euphoria) facilitating certain mental processes while retarding others. 12.3 pharmacokinetics upon absorption of morphine, oxidative dealkylation to produce nor-compounds appears to be the first step in the reaction sequence which imparts analgesia. morphine is conjugated in the liver to form the 3-glucuronide which passes into the bile and is reabsorbed and excreted in the urine. the atropine effect of the belladonna extract serves to eliminate morphine induced smooth muscle spasm without affecting the sedative analgesic action of powdered opium. 1

hildren, may result in respiratory depression or death [ see warnings and precautions (5.2) ]. instruct patients to take steps to store belladonna and opium suppositories securely and to dispose of unused belladonna and opium suppositories by returning to the pharmacy or delivering to an accredited disposal site. interactions with alcohol and other cns depressants inform patients that potentially serious additive effects may occur if belladonna and opium suppositories is used with alcohol or other cns depressants and not to use such drugs unless supervised by a health care provider [ see warnings and precautions (5.4), drug interactions (7) ]. serotonin syndrome inform patients that belladonna and opium suppositories could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications. [ see drug interactions 7 ]. adrenal insufficiency inform patients that belladonna and opium suppositories could cause adrenal insufficiency, a potentially life-threatening condition. adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. advise patients to seek medical attention if they experience a constellation of these symptoms [ see warnings and precautions (5.6) ]. pregnancy neonatal opioid withdrawal syndrome inform patients that 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 [ see warnings and precautions (5.3), use in specific populations (8.1) ]. embryo-fetal toxicity inform female patients of reproductive potential that belladonna and opium suppositories can (or may) cause fetal harm and to inform the prescriber of a known or suspected pregnancy [ see use in specific populations (8.1) ]. lactation advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. instruct nursing mothers to seek immediate medical care if they notice these signs [ see use in specific populations (8.2) ]. disposal of unused belladonna and opium suppositories advise patients to return unused suppositories to the pharmacy or deliver to an accredited disposal site.