methotrimeprazine

Absorption: Well absorbed after oral and IM administration. IV administration results in complete bioavailability.

Distribution: Enters CSF.

Metabolism/Excretion: Mostly metabolized by the liver. Some metabolites are active; 1% excreted unchanged by the kidneys.

Half-Life: 15–30 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO (plasma concentrations)	unknown	2.7–2.9 hr	8–12 hr
IM (analgesia)	unknown	20–40 min	8 hr (up to 24 hr in children)

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to methotrimeprazine, phenothiazines, or sulfites;
Blood dyscrasias;
Hepatic impairment;
Patients in coma or those who have overdosed on CNS depressants, including alcohol, analgesics, opioids, or sedative/hypnotics;
OB: Pregnancy.

Use Cautiously in:

History of seizures;
History of glaucoma or prostatic hypertrophy (↑ risk of anticholinergic adverse reactions);
Bradycardia, electrolyte abnormalities, congenital/acquired prolonged QT interval, or concurrent use of drugs that may prolong QT interval (↑ risk of serious arrhythmias);
Underlying cardiovascular disease, including stroke, arteriosclerosis, or thromboembolism (↑ risk of adverse cardiovascular effects);
Lactation: Safety and effectiveness not established in breastfeeding;
Geri: ↑risk of stroke, cognitive decline, and mortality in older adults with dementia.

Adv. Reactions/Side Effects ⬆ ⬇

CV: orthostatic hypotension, bradycardia, palpitations, tachycardia

EENT: nasal congestion

Endo: hyperglycemia, hyperprolactinemia

GI: constipation, abdominal discomfort, dry mouth, nausea, vomiting

GU: difficulty in urination

Hemat: blood dyscrasias

Local: pain at injection site

Neuro: amnesia, drowsiness, sedation, disorientation, euphoria, extrapyramidal reactions, headache, NEUROLEPTIC MALIGNANT SYNDROME (NMS), SEIZURES, slurred speech, tardive dyskinesia, weakness.

Misc: chills

Interactions ⬆ ⬇

Drug-drug:

↑CNS depression with other CNS depressants, including alcohol, antihistamines, antidepressants, opioids, or sedative/hypnotics; ↓ dose of these agents by 50% initially.
↑anticholinergic effects with antihistamines, antidepressants, phenothiazines, quinidine, disopyramide, atropine, or scopolamine; ↓ doses of atropine or scopolamine.
Reverses vasopressor effects of epinephrine; avoid concurrent use; if vasopressor required, use phenylephrine or norepinephrine.
↑risk of hypotension with acute ingestion of alcohol, nitrates, MAO inhibitors, or antihypertensives.
Succinylcholine may result in tachycardia, hypotension, CNS stimulation, delirium, and ↑ extrapyramidal symptoms.

Drug-Natural Products:

kava, skullcap, valerian, chamomile, or hops may ↑ risk of CNS depression.

Route/Dosage ⬆ ⬇

PO (Adults ): Minor conditions: 6–25 mg/day in 3 divided doses (if sedation occurs, use smaller daytime doses and a larger dose at bedtime); Nighttime sedative: 10–25 mg as a single bedtime dose; Psychoses/intense pain: 50–75 mg/day in 2–3 divided doses; may ↑ dose to desired effect (doses of ≥1 g/day have been used; if dose exceeds 100–200 mg/day, administer in divided doses and keep patient on bedrest).
PO (Children ): 0.25 mg/kg/day in 2–3 divided doses (not to exceed 40 mg/day in children <12 yr).
IM (Adults ): Postoperative analgesic adjunct: 10–25 mg every 8 hr; if given with opioids, ↓ opioid dose by 50%.
IM (Children ): Analgesia: 62.5–125 mcg (0.0625–0.125 mg)/kg/day single dose or divided doses; change to oral medication as soon as possible.
IV (Children ): Palliative care setting: 62.5 mcg (0.0625 mg)/kg/day as a slow infusion.

Availability ⬆ ⬇

Tablets: 2 mg; 5 mg; 25 mg; 50 mg
Solution for injection: 25 mg/mL

Assessment ⬆ ⬇

Assess type, location, and intensity of pain before and 30 min after administration.
Monitor BP frequently after injection. Orthostatic hypotension, fainting, syncope, and weakness frequently occur 10 min–12 hr after administration. Patient should remain supine for 6–12 hr after injection.
Assess weight and BMI initially and throughout therapy.
Observe patient carefully for extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill rolling, masklike face, shuffling gait, rigidity, tremors; dystonic: muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs). Usually occur only after prolonged or high-dose therapy. Usually resolve with dose ↓ or administration of antiparkinsonian agent.
Monitor for tardive dyskinesia (involuntary rhythmic movement of mouth, face, and extremities). Report immediately and discontinue therapy; may be irreversible.
Monitor for development of NMS (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). If signs/symptoms of NMS occur, discontinue methotrimeprazine immediately.
Methotrimeprazine potentiates the action of other CNS depressants but can be given in conjunction with modified doses of opioid analgesics for management of severe pain. This medication does not significantly depress respiratory status and can be useful where pulmonary reserve is low.
Monitor for signs/symptoms of hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).

Lab Test Considerations:

Monitor CBC before and periodically during therapy.
- Monitor liver function tests periodically throughout long-term (>30 days) therapy.
- Monitor blood glucose before and periodically during therapy. May cause hyperglycemia.
- Monitor serum prolactin before and periodically during therapy. May ↑ prolactin.

Implementation ⬆ ⬇

PO: Administer during day or only at night depending on indication.
IM: Do not inject SUBQ. Inject slowly into deep, well-developed muscle. Rotate injection sites.
Y-Site Compatibility:
- fentanyl
- hydromorphone
- methadone
- morphine
- sufentanil
Y-Site Incompatibility:
- heparin

IV Administration:

Intermittent Infusion: For patients on palliative care, may be infused as 0.0625 mg/kg/day in 250 mL of D5W. Rate: Infuse slowly, at 20–40 drops/min.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take medication as directed. Take missed doses as soon as remembered unless almost time for next dose; do not double dose.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise patient on how and when to ask for pain medication.
Advise patients to make position changes slowly and to remain recumbent for 6–12 hr after administration to minimize orthostatic hypotension.
May cause drowsiness. Caution patient to request assistance with ambulation and transfer and to avoid driving or other activities requiring alertness until response to the medication is known.
Advise patient to avoid taking alcohol or other CNS depressants concurrently with this medication.
Advise patient to use sunscreen and protective clothing when exposed to the sun. Extremes of temperature should also be avoided because this drug impairs body temperature regulation.
Advise patient to use frequent mouth rinses, good oral hygiene, and sugarless gum or candy to minimize dry mouth.
Advise patient to notify health care provider promptly if sore throat, fever, unusual bleeding or bruising, rash, weakness, tremors, dark-colored urine, clay-colored stools, or signs of blood clots (swelling, pain, and redness in an arm or leg that can be warm to touch; sudden chest pain; difficulty breathing; heart palpitations) occur.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Use should be avoided during 3rd trimester because of ↑ risk of agitation, hypotonia, tremor, somnolence, respiratory distress, and feeding disturbances in newborn.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇