Hyoscyamine

A03B - Belladonna and derivatives, plain ATC A03BA03 Small molecule Natural product

JFDA label: Neo-Allospasmin Pediatric Drp

Mechanism of Action

Blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS; increases cardiac output, dries secretions, antagonizes histamine and serotonin

Indications

Approved

Anesthesia
Antidote for anticholinesterase agent poisoning
Biliary and renal colic
Diagnostic procedures
GI disorders
Pancreatitis
Parkinsonism
Partial heart block
Preoperative antimuscarinic
Reversal of neuromuscular blockade and associated muscarinic effects
Rhinitis
Urinary system disorder

Contraindications

Source: Lexicomp

Hypersensitivity to belladonna alkaloids or any component of the formulation Absolute
myasthenia gravis Absolute
myocardial ischemia. Note: Some extended release products are not recommended in children Absolute
obstructive GI tract disease (eg, achalasia, pyloroduodenal stenosis), paralytic ileus, intestinal atony of elderly or debilitated patients, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis Absolute
obstructive uropathy (eg, bladder neck obstruction due to prostatic hypertrophy) Absolute
unstable cardiovascular status Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (3)

Not Known Flushing · palpitations · tachycardia

Nervous system disorders (13)

Not Known Amnesia (short-term) · ataxia · confusion (more common in elderly) · dizziness · drowsiness · excitement (more common in elderly) · fatigue · hallucination · headache · insomnia · nervousness · psychosis · speech disturbance

Renal and urinary disorders (4)

Not Known Decreased lactation · impotence · urinary hesitancy · urinary retention

Immune system disorders (1)

Not Known Hypersensitivity reaction

Gastrointestinal disorders (11)

Not Known Abdominal pain · ageusia · bloating · constipation · diarrhea · dysgeusia · dysphagia · heartburn · nausea · vomiting · xerostomia

Skin and subcutaneous tissue disorders (2)

Not Known Hypohidrosis · urticaria

Musculoskeletal and connective tissue disorders (1)

Not Known Weakness

Eye disorders (4)

Not Known Blurred vision · cycloplegia · increased intraocular pressure · mydriasis

General disorders and administration site conditions (1)

Not Known Fever

Dosing

Source: Lexicomp

Gastrointestinal disorders: Oral: Tablet, dispersible: Anaspaz, ED-SPAZ, NuLev, Symax FasTab: 0.125 to 0.25 mg every 4 hours or as needed; maximum: 1.5 mg/day Oscimin: 0.125 to 0.25 mg 3 to 4 times daily; may increase to every 4 hours as needed; maximum: 1.5 mg/day Tablet, extended release: Levbid: 0.375 to 0.75 mg every 12 hours; maximum: 1.5 mg/day Oscimin SR, Symax Duotab, Symax SR: 0.375 to 0.75 mg every 12 hours or 0.375 mg every 8 hours; maximum: 1.5 mg/day Tablet, regular release: Levsin: 0.125 to 0.25 mg every 4 hours or as needed; maximum: 1.5 mg/day Oscimin: 0.125 to 0.25 mg 3 to 4 times daily; may increase to every 4 hours as needed; maximum: 1.5 mg/day Tablet, sublingual (Levsin/SL, Oscimin, Symax SL): 0.125 to 0.25 mg 3 to 4 times daily; may increase to every 4 hours as needed; maximum: 1.5 mg/day Drops (Hyosyne [0.125 mg/mL]): 0.125 mg (1 mL) to 0.25 mg (2 mL) every 4 hours or as needed; maximum: 1.5 mg (12 mL) per day Elixir (Hyosyne [0.125 mg/5 mL]): 0.125 mg (5 mL) to 0.25 mg (10 mL) every 4 hours or as needed; maximum: 1.5 mg (60 mL) per day IM, IV, SubQ: 0.25 to 0.5 mg; may repeat as needed up to 4 times daily, at 4-hour intervals Diagnostic procedures: IV: 0.25 to 0.5 mg given 5 to 10 minutes prior to procedure Preanesthesia: IM, IV, SubQ: 5 mcg/kg given 30 to 60 minutes prior to induction of anesthesia or at the time preoperative opioids or sedatives are administered To reduce drug-induced bradycardia during surgery: IV: 0.125 mg; repeat as needed Reverse neuromuscular blockade: IM, IV, SubQ: 0.2 mg for every 1 mg neostigmine (or the physostigmine/pyridostigmine equivalent)

(For additional information see "Hyoscyamine: Pediatric drug information") Note: Oral dosage forms (drops and elixirs) are different (ie, 0.125 mg/mL [drops] and 0.125 mg/5 mL [elixir]); precaution should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented with corresponding product formulation. Gastrointestinal and urinary systemic spasms (including infant colic, biliary and renal colic): Infants and Children mL]): Do not exceed 6 doses in 24 hours 3.4 to drops) every 4 hours or as needed; maximum daily dose: 0.0825 mg (0.66 mL or 24 drops)/day 5 to drops) every 4 hours or as needed; maximum daily dose: 0.105 mg (0.84 mL or 30 drops)/day 7 to drops) every 4 hours or as needed; maximum daily dose: 0.12 mg (0.96 mL or 36 drops)/day ≥10 kg: 0.0275 mg (0.22 mL or 8 drops) every 4 hours or as needed; maximum daily dose: 0.165 mg (1.32 mL or 48 drops)/day Children 2 to Tablets (regular release [Levsin], sublingual [Levsin/SL], dispersible [ED-SPAZ, NuLev]): 0.0625 to 0.125 mg every 4 hours or as needed; maximum: 0.75 mg/day Drops (Hyosyne [0.125 mg/mL]): 0.03125 mg (0.25 mL) to 0.125 mg (1 mL) every 4 hours or as needed; maximum daily dose: 0.75 mg (6 mL)/day; do not exceed 6 doses in 24 hours Elixir (Hyosyne [0.125 mg/5 mL]): 10 to day 20 to day 40 to day ≥50 kg: 0.125 mg (5 mL) every 4 hours or as needed; maximum daily dose: 0.75 mg (30 mL)/day Children ≥12 years and Adolescents: Oral: Regular release tablets, dispersible tablets, sublingual tablets, elixir/drops, extended release tablets: Refer to adult dosing. Preanesthesia: Children >2 years and Adolescents: IV: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling, use with caution.

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

CNS effects

May cause drowsiness and/or blurred vision, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Diarrhea

May be a sign of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy; treatment should be discontinued if this occurs.

Heat prostration

May occur in the presence of increased environmental temperature; use caution in hot weather and/or exercise.

Oral effects

Prolonged use may lead to development of dental caries, periodontal disease, oral candidiasis, or discomfort due to decreased salivation.

Psychosis

Has been reported in patients with an extreme sensitivity to anticholinergic effects; usually resolves within 12-48 hours after discontinuation. Disease-related concerns:

Cardiovascular disease

Use with caution in patients with coronary artery disease, tachyarrhythmias, heart failure, or hypertension; evaluate tachycardia prior to administration. Use is contraindicated in patients with unstable cardiovascular status or myocardial ischemia.

Hiatal hernia

Use with caution in patients with hiatal hernia with reflux esophagitis.

Hyperthyroidism

Use with caution in patients with hyperthyroidism.

Neuropathy

Use with caution in patients with autonomic neuropathy.

Prostatic hyperplasia

Use with caution in patients with prostatic hyperplasia.

Renal impairment

Use with caution in patients with renal impairment. Special populations:

Pediatric

Use with caution in children with spastic paralysis or brain damage; may be more susceptible to anticholinergic effects. Dosage form specific issues:

Benzyl alcohol and derivatives

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Pregnancy & Lactation

Pregnancy

FDA category C

Crosses the placenta, effects to the fetus not known; use during pregnancy only if clearly needed.

Lactation

Avoid

Present in breast milk in trace amounts. May also suppress lactation. Breastfeeding is not recommended.

Chemistry & Properties

Formula	C17H23NO3
Molecular weight	289.37 g/mol
IUPAC name	[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] (2S)-3-hydroxy-2-phenylpropanoate
CAS	101-31-5
PubChem CID	154417
InChIKey	`RKUNBYITZUJHSG-FXUDXRNXSA-N`
logP	1.93 (XLogP 1.8)
Polar surface area	49.77 Å²
H-bond acceptors / donors	4 / 1
Drug-likeness (QED)	0.86
Lipinski violations	0

SMILES

CN1[C@@H]2CC[C@H]1C[C@@H](OC(=O)[C@H](CO)c1ccccc1)C2

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—
CYP2C9	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Potassium chloride	major
Potassium citrate	major
Topiramate	major
Zonisamide	major
Acebutolol	moderate
Acetylcholine	moderate
Aclidinium	moderate
Acrivastine	moderate
Alfentanil	moderate
Alimemazine	moderate
Amantadine	moderate
Ambenonium	moderate
Amitriptyline	moderate
Amoxapine	moderate
Arbutamine	moderate
Aripiprazole	moderate
Asenapine	moderate
Atenolol	moderate
Atropine	moderate
Azatadine	moderate
Belladonna	moderate
Benzatropine	moderate
Benzhydrocodone	moderate
Betaxolol	moderate
Bethanechol	moderate
Biperiden	moderate
Bisoprolol	moderate
Botulinum Toxin Type B	moderate
Botulinum toxin type A	moderate
Brexanolone	moderate
Brexpiprazole	moderate
Brompheniramine	moderate
Buprenorphine	moderate
Butorphanol	moderate
Carbamoylcholine (ophthalmic)	moderate
Carbinoxamine	moderate
Cariprazine	moderate
Carteolol	moderate
Carvedilol	moderate
Cevimeline	moderate

Showing 40 of 100+.

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Neo-Allospasmin Pediatric Drp	Injection 0.125 mg/ml	15 ml	The Arab Pharmaceutical Manufactruing Co.	0.810