methotrimeprazine

Absorption: Well absorbed after PO/IM administration. IV administration results in complete bioavailability.

Distribution: Enters CSF and crosses the placenta. Minimal amounts enter breast milk.

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 (blood levels)	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:

Blood dyscrasias;
Hepatic impairment;
Hypersensitivity to methotrimeprazine, phenothiazines or sulfites;
Comatose patients or those who have overdosed on CNS depressants including alcohol, analgesics, opioids, or sedative/hypnotics;
OB: Third-trimester use may result in agitation, hypotonia, tremor, somnolence, respiratory distress, and feeding disturbances in newborn and should be avoided.

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);
Geri: Initial dosage ↓ recommended, ↑ risk of death in elderly patients with dementia;
Lactation: Safety not established;
Pedi: Safety not established.

Adv. Reactions/Side Effects ⬆ ⬇

CNS: amnesia, drowsiness, excess sedation, disorientation, euphoria, extrapyramidal reactions, headache, NEUROLEPTIC MALIGNANT SYNDROME, SEIZURES, slurred speech, tardive dyskinesia, weakness.

EENT: nasal congestion

CV: orthostatic hypotension, bradycardia, palpitations, tachycardia

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

GU: difficulty in urination

Endo: hyperglycemia, hyperprolactinemia

Hemat: blood dyscrasias

Local: pain at injection site

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 concurrent 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.
Concurrent use with succinylcholine may result in tachycardia, hypotension, CNS stimulation, delirium, and ↑ extrapyramidal symptoms.

Drug-Natural Products:

Concomitant use of kava, valerian, skullcap, chamomile, or hops↑ 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); Night time sedative: 10–25 mg as a single bedtime dose; Psychoses/intense pain: 50–75 mg/day in 2–3 divided doses, dose may be titrated upward to desired effect (doses of 1 g/day have been used, if daily dose exceeds 100–200 mg, administer in divided doses and keep patient at 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 in 250 mL of 5% dextrose solution as a slow infusion (20–40 drops/min).

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 from 10 min to 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, mask-like 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 decrease 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 neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Discontinue methotrimeprazine and notify health care professional immediately if these symptoms occur.
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 symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).

Lab Test Considerations:

Monitor CBC prior to and periodically during therapy and liver function tests should be evaluated periodically throughout long-term (>30 days) therapy.
- Monitor blood glucose prior to and periodically during therapy. May cause hyperglycemia.
- Monitor serum prolactin prior to and periodically during therapy. May cause ↑ serum prolactin levels.

Implementation ⬆ ⬇

PO: May be administered during day or only at night depending on indication.
IM: Do not inject SUBQ. Inject slowly into deep, well-developed muscle. Rotate injection sites.
Intermittent Infusion: For patients in palliative care, may be infused as 0.0625 mg/kg/day in 250 mL of D5W.
Rate: Infuse slowly 20–40 drops per min.
Y-Site Compatibility:
- fentanyl
- hydromorphone
- methadone
- morphine
- sufentanil
Y-Site Incompatibility:
- heparin

Patient/Family Teaching ⬆ ⬇

Instruct patient on how and when to ask for pain medication.
Instruct patient 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 read Patient Information leaflet prior to starting therapy and with each Rx refill in case of changes.
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 notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Caution 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.
Instruct patient to use frequent mouth rinses, good oral hygiene, and sugarless gum or candy to minimize dry mouth.
Instruct patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, rash, weakness, tremors, dark-colored urine, or 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇