PROVOCHOLINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROVOCHOLINE (PROVOCHOLINE).
Parasympathomimetic agent that acts as a direct cholinergic agonist at muscarinic receptors, increasing exocrine gland secretion.
| Metabolism | Primarily metabolized by acetylcholinesterase. |
| Excretion | Primarily renal excretion of unchanged drug and inactive metabolites. Approximately 80-90% of administered dose is excreted renally. No significant biliary or fecal elimination. |
| Half-life | Terminal elimination half-life is 1-2 hours in patients with normal renal function. However, due to rapid hydrolysis by plasma and tissue cholinesterases, the actual duration of effect is brief (minutes). Clinical context: half-life may be prolonged in patients with reduced cholinesterase activity or renal impairment. |
| Protein binding | Very low protein binding (<5%). Does not significantly bind to albumin or other plasma proteins. |
| Volume of Distribution | Approximately 0.1-0.2 L/kg. Small Vd indicates limited extravascular distribution, consistent with a quaternary ammonium compound that does not readily cross cell membranes or the blood-brain barrier. |
| Bioavailability | Subcutaneous: approximately 90-100%. Oral: Very low (<2%) due to extensive presystemic metabolism by cholinesterases in the gastrointestinal tract and liver. Not administered orally. Inhalation: Variable, but effective locally; systemic absorption is minimal. |
| Onset of Action | Subcutaneous administration: Onset within 1-2 minutes. Peak effect at 5-10 minutes. Intramuscular: Slightly slower onset. Oral: Not clinically used due to extensive first-pass metabolism. Inhalation: Onset within 30 seconds to 2 minutes. |
| Duration of Action | Subcutaneous: Duration 10-30 minutes. Intravenous: Even shorter (5-15 minutes). Duration is limited by rapid hydrolysis. Clinical note: Effects dissipate quickly; continuous infusion may be required for sustained effect. |
Subcutaneous: 2.5-5 mg; if no response, repeat with 5-10 mg; maximum single dose 10 mg.
| Dosage form | FOR SOLUTION |
| Renal impairment | No specific guidelines; use caution in severe renal impairment. |
| Liver impairment | No specific guidelines; use caution in severe hepatic impairment. |
| Pediatric use | Safety and efficacy not established; use not recommended. |
| Geriatric use | Use with caution due to potential for increased sensitivity and comorbidities; consider starting at lower end of dosing range. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROVOCHOLINE (PROVOCHOLINE).
| Breastfeeding | No human data on excretion in breast milk. Methacholine is rapidly hydrolyzed by plasma cholinesterases; systemic absorption after inhalation is minimal. M/P ratio is unknown. Caution is advised, but risk to nursing infant is likely low given rapid metabolism and low bioavailability. |
| Teratogenic Risk | Pregnancy Category C. Based on animal studies and limited human data, PROVOCHOLINE (methacholine) is not expected to increase the risk of major congenital malformations. However, bronchial provocation testing is generally avoided during pregnancy due to potential maternal hypoxia and fetal distress. First trimester: theoretical risk from maternal hypoxia; second and third trimesters: risk of preterm labor and fetal hypoxia if severe bronchospasm occurs. |
■ FDA Black Box Warning
Severe asthma or wheezing; administration to patients with asthma can cause fatal bronchospasm.
| Serious Effects |
Asthma, COPD, severe cardiac disease, recent myocardial infarction, hypotension, hypertension, hyperthyroidism, epilepsy, Parkinson's disease, peptic ulcer, gastrointestinal or urinary obstruction, pregnancy (Category C).
| Precautions | Should be administered only by trained personnel; emergency resuscitative equipment must be immediately available; may cause bronchoconstriction, bradycardia, hypotension; use caution in patients with cardiovascular disease, epilepsy, hyperthyroidism, peptic ulcer, urinary obstruction. |
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| Fetal Monitoring | Maternal: pulmonary function tests (FEV1), oxygen saturation, heart rate and rhythm, blood pressure; signs of bronchospasm or excessive cholinergic effects (bradycardia, hypotension, increased secretions). Fetal: heart rate monitoring if testing performed during pregnancy; assess for signs of fetal distress if maternal hypoxia occurs. |
| Fertility Effects | No significant data on effects on male or female fertility. Inhalation challenge tests are single-use diagnostic procedures and are unlikely to have lasting effects on reproduction. |