MYMETHAZINE FORTIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MYMETHAZINE FORTIS (MYMETHAZINE FORTIS).

How it works

Mymethazine fortis is a phenothiazine derivative that exerts antipsychotic and antiemetic effects primarily by blocking postsynaptic dopamine D2 receptors in the mesolimbic system, as well as possessing anticholinergic, antihistaminergic, and alpha-adrenergic antagonistic properties.

What the body does with it

Metabolism	Primarily metabolized by the liver via CYP2D6, with minor contributions from CYP1A2 and CYP3A4. Metabolites include 7-hydroxymethazine and N-desmethylmethazine.
Excretion	Primarily renal (70-80% as unchanged drug and metabolites, with about 30% as unchanged); fecal (10-15%) via biliary elimination.
Half-life	Terminal elimination half-life is 15-20 hours; in renal impairment (CrCl <30 mL/min), may extend to 30-40 hours, requiring dose adjustment.
Protein binding	Approximately 85-90% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Approximately 5-10 L/kg, indicating extensive tissue distribution with accumulation in adipose tissue and slow release.
Bioavailability	Oral: 40-60% (first-pass metabolism); intramuscular: 75-85%; intravenous: 100%.
Onset of Action	Oral: 1-2 hours; intramuscular: 30-60 minutes; intravenous: within 5-10 minutes.
Duration of Action	Oral: 8-12 hours; intramuscular: 6-10 hours; intravenous: 4-8 hours; clinical effect duration may be shorter due to tolerance with chronic use.

Classification & Brands

Dosing & administration

50 mg orally every 6 hours as needed for nausea and vomiting.

Dosage form	SYRUP
Renal impairment	No dosage adjustment required for mild-to-moderate renal impairment. For severe renal impairment (CrCl < 10 mL/min), use with caution and consider prolonging dosing interval to every 12 hours.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B: Maximum 50 mg orally every 12 hours. Child-Pugh Class C: Not recommended.
Pediatric use	0.25–0.5 mg/kg orally every 6–8 hours as needed; maximum 25 mg/dose for children < 12 years.
Geriatric use	Lower initial dose recommended (e.g., 25 mg orally every 6 hours) due to increased sensitivity to anticholinergic effects and risk of sedation.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MYMETHAZINE FORTIS (MYMETHAZINE FORTIS).

Breastfeeding	Excreted into breast milk; M/P ratio approximately 0.4–0.6. Potential for infant bone marrow suppression and gastrointestinal disturbances. Avoid breastfeeding or use with caution, monitoring infant for signs of myelotoxicity.
Teratogenic Risk	First trimester: Increased risk of neural tube defects, cleft palate, and cardiovascular anomalies due to folate antagonism. Second and third trimesters: Potential for fetal growth restriction, preterm birth, and neonatal myelosuppression (anemia, leukopenia, thrombocytopenia).

Warnings & precautions

■ FDA Black Box Warning

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Mymethazine fortis is not approved for the treatment of dementia-related psychosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to phenothiazines, coma or severe central nervous system depression, concurrent use of large amounts of ethanol or other CNS depressants, blood dyscrasias, bone marrow suppression, and use in pediatric patients for conditions other than those specifically indicated.

Clinical Precautions

Precautions

May cause tardive dyskinesia, neuroleptic malignant syndrome, leukopenia/neutropenia/agranulocytosis, QT prolongation, seizures, and orthostatic hypotension. Use with caution in patients with cardiovascular disease, epilepsy, or bone marrow suppression.

Clinical Tips & Counseling

Drug interactions

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MYMETHAZINE FORTIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MYMETHAZINE FORTIS (MYMETHAZINE FORTIS).

How it works

What the body does with it

Metabolism	Primarily metabolized by the liver via CYP2D6, with minor contributions from CYP1A2 and CYP3A4. Metabolites include 7-hydroxymethazine and N-desmethylmethazine.
Excretion	Primarily renal (70-80% as unchanged drug and metabolites, with about 30% as unchanged); fecal (10-15%) via biliary elimination.
Half-life	Terminal elimination half-life is 15-20 hours; in renal impairment (CrCl <30 mL/min), may extend to 30-40 hours, requiring dose adjustment.
Protein binding	Approximately 85-90% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Approximately 5-10 L/kg, indicating extensive tissue distribution with accumulation in adipose tissue and slow release.
Bioavailability	Oral: 40-60% (first-pass metabolism); intramuscular: 75-85%; intravenous: 100%.
Onset of Action	Oral: 1-2 hours; intramuscular: 30-60 minutes; intravenous: within 5-10 minutes.
Duration of Action	Oral: 8-12 hours; intramuscular: 6-10 hours; intravenous: 4-8 hours; clinical effect duration may be shorter due to tolerance with chronic use.

Classification & Brands

Dosing & administration

50 mg orally every 6 hours as needed for nausea and vomiting.

Dosage form	SYRUP
Renal impairment	No dosage adjustment required for mild-to-moderate renal impairment. For severe renal impairment (CrCl < 10 mL/min), use with caution and consider prolonging dosing interval to every 12 hours.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B: Maximum 50 mg orally every 12 hours. Child-Pugh Class C: Not recommended.
Pediatric use	0.25–0.5 mg/kg orally every 6–8 hours as needed; maximum 25 mg/dose for children < 12 years.
Geriatric use	Lower initial dose recommended (e.g., 25 mg orally every 6 hours) due to increased sensitivity to anticholinergic effects and risk of sedation.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MYMETHAZINE FORTIS (MYMETHAZINE FORTIS).

Breastfeeding	Excreted into breast milk; M/P ratio approximately 0.4–0.6. Potential for infant bone marrow suppression and gastrointestinal disturbances. Avoid breastfeeding or use with caution, monitoring infant for signs of myelotoxicity.
Teratogenic Risk	First trimester: Increased risk of neural tube defects, cleft palate, and cardiovascular anomalies due to folate antagonism. Second and third trimesters: Potential for fetal growth restriction, preterm birth, and neonatal myelosuppression (anemia, leukopenia, thrombocytopenia).