Hyoscyamine Sulfate

The following dosing information is available for HYOSCYAMINE SULFATE (hyoscyamine sulfate):

Dosing
Administration
HYOSCYAMINE SULFATE
HYOSCYAMINE SULFATE

The usual adult oral dosage of hyoscyamine is 0.15-0.3 mg, given up to 4 times daily.

If the drug is used in older pediatric patients, dosage should be reduced in proportion to age and weight.

Dosage should be carefully titrated according to the condition, severity of symptoms, and the individual patient's response and tolerance to the drug. Geriatric patients may be more sensitive to the effects of the drug at usual adult dosages.

The usual dosage of hyoscyamine sulfate (as conventional, sublingual, or orally disintegrating tablets or as an oral solution or elixir) in adults and pediatric patients 12 years of age or older is 0.125-0.25 mg, given orally or sublingually every 4 hours or as needed, not to exceed a total dosage of 1.5

mg in a 24-hour period. One manufacturer (Symax(R) SL) recommends an oral or sublingual dosage of 0.125-0.25

mg 3 or 4 times daily. Alternatively, in adults and pediatric patients 12 years of age or older, 0.375-0.75

mg every 12 hours, not to exceed a total dosage of 1.5 mg in a 24-hour period, may be given orally as extended-release capsules or tablets. If dosage adjustment is required, extended-release capsules and tablets may be administered at a dosage of 0.375

mg every 8 hours. As with other antimuscarinics, higher than recommended dosage may be required for therapeutic effect. Dosage should be carefully titrated until therapeutic effect is achieved or adverse effects become intolerable, using the lowest possible effective dosage.

For pediatric patients 2-11 years of age, the usual dosage of hyoscyamine sulfate (as conventional, sublingual, or orally disintegrating tablets or as an oral solution) is 31.25-125 mcg (0.03125-0.125 mg) given orally or sublingually every 4 hours or as needed, not to exceed a total dosage of 750 mcg in a 24-hour period. One manufacturer (Symax(R) SL) recommends that pediatric patients 2-11 years of age receive an oral or sublingual dosage of 62.5-125

mcg (0.0625-0.125 mg) 3 or 4 times daily. Alternatively, some manufacturers state that pediatric patients 2-11 years of age may receive a dosage of 375 mcg (0.375 mg) every 12 hours (as extended-release capsules or tablets), not to exceed 750 mcg in a 24-hour period. Manufacturers of hyoscyamine sulfate elixir recommend that dosage in patients 2-11 years of age be determined based on body weight (see Table 1).

Table 1. Weight-based Dosing of Hyoscyamine Sulfate Elixir in Pediatric Patients 2-11 Years of Age

Body Weight Usual Dosage Maximum Dosage in a 24-hour Period 10 kg (22 lb) 1.25 mL (31.25 mcg) 7.5 mL (187.5 mcg) every 4 hours or as needed 20 kg (44 lb) 2.5

mL (62.5 mcg) every 15 mL (375 mcg) 4 hours or as needed 40 kg (88 lb) 3.75 mL (93.75 mcg) 22.5 mL (562.5 mcg) every 4 hours or as needed 50 kg (110 lb) 5 mL (125 mcg) every 4 30 mL (750 mcg) hours or as needed

For pediatric patients younger than 2 years of age, manufacturers of hyoscyamine sulfate oral solution (drops) recommend weight-based dosing (see Table 2).

Table 2. Weight-based Dosing of Hyoscyamine Sulfate Oral Solution (Drops) in Pediatric Patients Younger Than 2 Years of Age

Body Weight Usual Dosage Maximum Dosage in a 24-hour Period 3.4 kg (7.5 lb) 4 drops (15.63 mcg) 24 drops (93.75 mcg) every 4 hours or as needed 5 kg (11 lb) 5 drops (19.53 mcg) 30 drops (117.19 mcg) every 4 hours or as needed 7 kg (15 lb) 6 drops (23.44 mcg) 36 drops (140.63 mcg) every 4 hours or as needed 10 kg (22 lb) 8 drops (31.25 mcg) 48 drops (187.5 mcg) every 4 hours or as needed

Using the dropper provided by the manufacturer, which is calibrated to deliver approximately 32 drops/mL.

The usual IV, IM, or subcutaneous dosage of hyoscyamine sulfate for the treatment of GI disorders in adults is 0.25-0.5 mg every 4 hours, 2-4 times daily.

For the treatment of acute symptoms associated with GI disorders, a single parenteral dose of 0.25-0.5 mg may be sufficient.

Dosage should be adjusted according to the individual patient's response and tolerance.

For diagnostic procedures (e.g., endoscopy, hypotonic duodenography) in adults, 0.25-0.5 mg of hyoscyamine sulfate is administered by IV, IM, or subcutaneous injection 5-10 minutes prior to the diagnostic procedure.

As a preoperative medication in adults and pediatric patients older than 2 years of age, the usual dose of hyoscyamine sulfate is 5 mcg (0.005 mg) per kg given IV, IM, or subcutaneously 30-60 minutes prior to the anticipated time of induction of anesthesia or at the time other preanesthetic medications (e.g., opiates, sedatives) are administered. For intraoperative use to reverse drug-induced bradycardia, hyoscyamine sulfate is administered IV in 0. 125-mg increments, repeated as necessary.

To block adverse muscarinic effects of anticholinesterase agents (i.e., neostigmine, physostigmine, pyridostigmine) when these agents are used to reverse the neuromuscular blockade produced by curariform agents, the usual IV dose of hyoscyamine sulfate in adults and pediatric patients older than 2 years of age is 0.2 mg for each 1 mg of neostigmine methylsulfate or the equivalent dose of physostigmine salicylate or pyridostigmine bromide administered; hyoscyamine sulfate is administered concurrently with (but in a separate syringe) or a few minutes before the anticholinesterase agent. In the presence of bradycardia, hyoscyamine sulfate should be given IV before the anticholinesterase agent to increase the pulse rate to about 80 beats/minute.

For the treatment of muscarinic toxicity resulting from exposure to anticholinesterase compounds (e.g., organophosphate pesticides), the usual initial adult dose of hyoscyamine sulfate is 1-2 mg, preferably administered IV. Additional 1-mg doses may be administered IM or IV every 3-10 minutes until muscarinic signs and symptoms subside and repeated if they reappear. Up to 25 mg of the drug may be required during the first 24 hours of therapy.

Subsequently, 0.5-1 mg may be administered orally at intervals of several hours as maintenance therapy until signs and symptoms completely subside. A cholinesterase reactivator (e.g., pralidoxime) is administered concomitantly with antimuscarinic therapy.

Hyoscyamine is administered orally. Hyoscyamine sulfate is usually administered orally or sublingually. Hyoscyamine sulfate also may be administered by IV, IM, or subcutaneous injection when oral or sublingual administration is not feasible or when rapid therapeutic effect is necessary.

Hyoscyamine sulfate is commercially available as conventional (immediate-release) tablets, extended-release capsules and tablets, oral solutions (drops), elixirs, sublingual tablets, orally disintegrating tablets, and injection. Immediate-release preparations of hyoscyamine sulfate (conventional, sublingual, or orally disintegrating tablets; oral solutions (drops); elixirs) generally are administered orally or sublingually 3-6 times daily. Extended-release preparations of hyoscyamine sulfate should not be crushed or chewed.

Symax(R) SR and Symax(R) DuoTab(R) tablets should be swallowed whole, while Levbid(R) tablets and certain generic preparations are scored and may be broken in order to titrate dosage. Extended-release preparations generally are administered every 12 hours, but preparations that are not scored may be administered every 8 hours if dosage adjustment is required. Patients should be advised that extended-release preparations may not completely disintegrate and fragments may be excreted in stools in some patients.

Sublingual tablets of hyoscyamine sulfate (i.e., Levsin(R)/SL, Symax(R) SL, generic preparations) may be administered sublingually or orally. Certain sublingual tablets (e.g., Levsin(R)/SL, certain generic preparations) also may be chewed. The manufacturers of Levsin(R)/SL and certain generic preparations state that oral administration of the sublingual tablets results in similar pharmacologic effects as sublingual administration, although the onset may not be as rapid.

Orally disintegrating tablets of hyoscyamine sulfate (i.e., NuLev(R), Symax(R) FasTab(R), generic preparations) are administered by placing a tablet on the tongue to dissolve and be swallowed with the saliva; orally disintegrating tablets may be administered with or without water. Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that each 0.125-mg NuLev(R), Symax(R) FasTab(R), or generic hyoscyamine sulfate (marketed by Ethex) orally disintegrating tablet contains aspartame (NutraSweet(R)), which is metabolized in the GI tract to provide about 1.7,

4.5, or 0.5 mg, respectively, of phenylalanine following oral administration.

Because antacids may decrease absorption of oral hyoscyamine sulfate when these drugs are administered simultaneously, most manufacturers recommend administration of hyoscyamine sulfate before meals and administration of antacids postprandially. One manufacturer recommends routine administration of hyoscyamine sulfate (Symax(R) formulations) 30-60 minutes before meals. Hyoscyamine sulfate injection may be administered by IV, IM, or subcutaneous injection without prior dilution. Parenteral hyoscyamine sulfate solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Dosing information for HYOSCYAMINE SULFATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
HYOSCYAMINE SULF 0.125 MG TAB	Maintenance	Adults take 1 tablet (0.125 mg) by oral route every 4 hours as needed

Generic dosing information for HYOSCYAMINE SULFATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
HYOSCYAMINE SULF 0.125 MG TAB	Maintenance	Adults take 1 tablet (0.125 mg) by oral route every 4 hours as needed
HYOSCYAMINE 0.125 MG ODT	Maintenance	Adults place 1 tablet (0.125 mg) by sublingual route every 4 hours as needed

The following drug interaction information is available for HYOSCYAMINE SULFATE (hyoscyamine sulfate):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Pramlintide/Anticholinergics; Antispasmodics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Pramlintide slows gastric emptying. Anticholinergics and antispasmodics may result in additive or synergistic effects on gastric emptying. CLINICAL EFFECTS: Concurrent use of pramlintide and anticholinergics or antispasmodics may result in additive or synergistic effects on gastric emptying. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of pramlintide states that pramlintide therapy should not be considered in patients requiring the use of drugs that alter gastrointestinal motility.(1) Patients receiving anticholinergics and antispasmodics should be evaluated for signs of systemic effects which may include constipation. DISCUSSION: Patients using drugs that alter gastrointestinal motility have not been studied in clinical trials for pramlintide.(1) Constipation has been reported as a side effect of anticholinergics and antispasmodics.	SYMLINPEN 120, SYMLINPEN 60

Drug Interaction

Drug Names

Pramlintide/Anticholinergics; Antispasmodics

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Pramlintide slows gastric emptying. Anticholinergics and antispasmodics may result in additive or synergistic effects on gastric emptying.

CLINICAL EFFECTS: Concurrent use of pramlintide and anticholinergics or antispasmodics may result in additive or synergistic effects on gastric emptying.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of pramlintide states that pramlintide therapy should not be considered in patients requiring the use of drugs that alter gastrointestinal motility.(1) Patients receiving anticholinergics and antispasmodics should be evaluated for signs of systemic effects which may include constipation.

DISCUSSION: Patients using drugs that alter gastrointestinal motility have not been studied in clinical trials for pramlintide.(1) Constipation has been reported as a side effect of anticholinergics and antispasmodics.

SYMLINPEN 120, SYMLINPEN 60

There are 6 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Solid Oral Potassium Tablets/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with anticholinergics may result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17)	KLOR-CON 10, KLOR-CON 8, KLOR-CON M10, KLOR-CON M15, KLOR-CON M20, POTASSIUM CHLORIDE, POTASSIUM CITRATE ER, UROCIT-K
Solid Oral Potassium Capsules/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16)) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with anticholinergics may result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. The lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17)	POTASSIUM CHLORIDE
Secretin/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Anticholinergic drugs may result in an incorrect secretin stimulation test result.(1) CLINICAL EFFECTS: Concurrent use of anticholinergic drugs may impact the accuracy of the secretin stimulation test.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of human secretin states concurrent use of anticholinergic drugs at the time of stimulation testing may cause the patient to be hyporesponsive to the testing and suggest false positive results for pancreatic disease. The manufacturer recommends discontinuing anticholinergic drugs at least 5 half-lives prior to stimulation testing. Consider additional testing and clinical assessment for diagnosis.(1) DISCUSSION: Concurrent use of anticholinergic drugs may impact the accuracy of the secretin stimulation test.(1)	CHIRHOSTIM
Clozapine/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine has potent anticholinergic properties and inhibits serotonin receptors, including 5-HT3.(1-4) Both of these properties may cause inhibition of gastrointestinal (GI) smooth muscle contraction, resulting in decreased peristalsis.(3,4) These effects may be compounded by concurrent use of anticholinergic agents.(1-6) CLINICAL EFFECTS: Concurrent use of clozapine with other anticholinergic agents may increase the risk of constipation (common) and serious bowel complications (uncommon), including complete bowel obstruction, fecal impaction, paralytic ileus and intestinal ischemia or infarction.(1-6) PREDISPOSING FACTORS: The risk for serious bowel complications is higher with increasing age, higher frequency of constipation, and in patients on higher doses of clozapine or multiple anticholinergic agents.(1,5) PATIENT MANAGEMENT: Avoid the use of other anticholinergic agents with clozapine.(1-6) If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(2) Consider a prophylactic laxative in those with a history of constipation or bowel obstruction.(2) Review patient medication list for other anticholinergic agents. When possible, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly. Counsel the patient about the importance of maintaining adequate hydration. Encourage regular exercise and eating a high-fiber diet.(2) DISCUSSION: In a prospective cohort study of 26,720 schizophrenic patients in the Danish Central Psychiatric Research Registry, the odds ratio (OR) for ileus was 1.99 with clozapine and 1.48 with anticholinergics. The OR for fatal ileus was 6.73 with clozapine and 5.88 with anticholinergics. Use of anticholinergics with 1st generation antipsychotics (FGA) increased the risk of ileus compare to FGA alone, but this analysis was not done with clozapine.(5) A retrospective cohort study of 24,970 schizophrenic patients from the Taiwanese National Health Insurance Research Database found that the hazard ratio (HR) for clozapine-induced constipation increased from 1.64 when clozapine is used alone, to 2.15 when used concomitantly with anticholinergics. However, there was no significant difference in the HR for ileus when clozapine is used with and without anticholinergics (1.95 and 2.02, respectively).(6) In the French Pharmacovigilance Database, 7 of 38 cases of antipsychotic-associated ischemic colitis or intestinal necrosis involved clozapine, and 5 of these cases involved use of concomitant anticholinergic agents. Three patients died, one of whom was on concomitant anticholinergics.(3) In a case series, 4 of 9 cases of fatal clozapine-associated GI dysfunction involved concurrent anticholinergic agents.(4)	CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ
Eluxadoline/Anticholinergics; Opioids SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Eluxadoline is a mixed mu-opioid and kappa-opioid agonist and delta-opioid antagonist and may alter or slow down gastrointestinal transit.(1) CLINICAL EFFECTS: Constipation related adverse events that sometimes required hospitalization have been reported, including the development of intestinal obstruction, intestinal perforation, and fecal impaction.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid use with other drugs that may cause constipation. If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(1) Instruct patients to stop eluxadoline and immediately contact their healthcare provider if they experience severe constipation. Loperamide may be used occasionally for acute management of severe diarrhea, but must be discontinued if constipation develops.(1) DISCUSSION: In phase 3 clinical trials, constipation was the most commonly reported adverse reaction (8%). Approximately 50% of constipation events occurred within the first 2 weeks of treatment while the majority occurred within the first 3 months of therapy. Rates of severe constipation were less than 1% in patients receiving eluxadoline doses of 75 mg and 100 mg.(1)	VIBERZI
Glucagon (Diagnostic)/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility.(1) CLINICAL EFFECTS: Concurrent use of glucagon with anticholinergic agents may increase the risk of gastrointestinal hypomotility, including constipation and bowel complications.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of glucagon as a diagnotic aid is not recommended with the use of anticholinergic agents.(1) If concurrent use is necessary, evaluate the patient's bowel function. Monitor for symptoms of constipation and gastrointestinal hypomotility. DISCUSSION: Both glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility and increase the risk of gastrointestinal adverse effects.(1)	GLUCAGON HCL

There are 4 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Select Antipsychotics;Select Phenothiazines/Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Multiple mechanisms may be involved: 1. additive peripheral and CNS blockade of muscarinic receptors. 2. anticholinergic-induced inhibition of gastrointestinal absorption of phenothiazines. 3. antagonism of the dopamine blocking effects of selected antipsychotics and phenothiazines. CLINICAL EFFECTS: The dopamine blocking effects of selected antipsychotic agents or phenothiazines may be decreased while anticholinergic adverse effects may be increased. PREDISPOSING FACTORS: The risk for severe anticholinergic toxicities, e.g. delirium, hyperthermia, paralytic ileus is increased in the elderly and in patients on multiple anticholinergic agents. PATIENT MANAGEMENT: Anticholinergic agents may be required to treat or prevent antipsychotic induced extrapyramidal symptoms. When other indications lead to co-prescribing of the combination, assess patient response to the combination. Review patient medication list for other anticholinergic agents. When needed, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly. DISCUSSION: Although numerous studies have been published regarding a possible interaction between phenothiazines and anticholinergics, the earlier reports were not double-blind or placebo controlled and patients may have received other drugs concomitantly. These earlier investigations reported increased side effects as well as increased, decreased and no effect on the therapeutic outcome. Double-blind studies have also reported conflicting results. Anticholinergic therapy varied from having no effect on phenothiazine concentration or patient outcome, to increasing phenothiazine levels. The discrepancies reported may be due to interpatient variability including age of the patient, type and duration of illness and treatment setting.	ADASUVE, CHLORPROMAZINE HCL, LOXAPINE, PERPHENAZINE, PERPHENAZINE-AMITRIPTYLINE, PHENERGAN, PROMETHAZINE HCL, PROMETHAZINE HCL-0.9% NACL, PROMETHAZINE VC, PROMETHAZINE-CODEINE, PROMETHAZINE-DM, PROMETHAZINE-PHENYLEPHRINE HCL, PROMETHEGAN, THIORIDAZINE HCL, THIORIDAZINE HYDROCHLORIDE, TRIFLUOPERAZINE HCL
Oral Itraconazole; Ketoconazole/Hyoscyamine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Hyoscyamine delays gastric emptying and may increase gastric pH, thereby decreasing the absorption of orally administered itraconazole and ketoconazole.(1) CLINICAL EFFECTS: Simultaneous administration of hyoscyamine may result in decreased levels and effectiveness of oral itraconazole and ketoconazole.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Oral itraconazole and ketoconazole should be administered at least 2 hours after hyoscyamine.(1) DISCUSSION: Hyoscyamine delays gastric emptying and may increase gastric pH, decreasing the amount of azole antifungal absorption.(1)	ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KETOCONAZOLE, SPORANOX, TOLSURA
Zonisamide/Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Zonisamide can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2) CLINICAL EFFECTS: Concurrent use of zonisamide with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The UK and US manufacturers of zonisamide state that caution should be used in adults when zonisamide is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity.(1-2) Pediatric and adolescent patients must not take anticholinergic agents (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered. DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment and resulted in death.(1)	ZONEGRAN, ZONISADE, ZONISAMIDE
Topiramate/Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Topiramate can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2) CLINICAL EFFECTS: Concurrent use of topiramate with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The manufacturer of topiramate states that caution should be used when topiramate is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered. DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment.(1) A 64-year old woman developed non-exertional hyperthemia while taking multiple psychiatric medications with topiramate.(2)	EPRONTIA, PHENTERMINE-TOPIRAMATE ER, QSYMIA, TOPAMAX, TOPIRAMATE, TOPIRAMATE ER, TOPIRAMATE ER SPRINKLE, TROKENDI XR

Contraindication List
Achalasia of esophagus
Atony of colon
Benign prostatic hyperplasia
Bladder outflow obstruction
Glaucoma
Hypovolemic shock
Myasthenia gravis
Paralytic ileus
Pyloroduodenal obstruction
Severe ulcerative colitis
Toxic megacolon

Moderate List
Autonomic neuropathy
Cardiac arrhythmia
Chronic heart failure
Coronary artery disease
Gastroesophageal reflux disease
Hiatal hernia
High fever >101 degrees fahrenheit
Hypertension
Hyperthyroidism
Kidney disease with reduction in glomerular filtration rate (GFr)