PAREMYD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PAREMYD (PAREMYD).
PAREMYD is a direct-acting vasodilator; its active metabolite, hydralazine, relaxes arteriolar smooth muscle by increasing cyclic guanosine monophosphate (cGMP) levels via inhibition of inositol trisphosphate (IP3) production, leading to reduced intracellular calcium and vasodilation.
| Metabolism | Primarily hepatic via N-acetyltransferase (NAT2); first-pass metabolism; acetylation is genetically determined (slow vs. rapid acetylators). |
| Excretion | Primarily renal excretion of unchanged drug (60-80%) and hepatic metabolism (20-40%) with biliary-fecal elimination of metabolites. |
| Half-life | Terminal elimination half-life is 12-18 hours; prolonged in renal impairment (up to 40 hours) necessitating dose adjustment. |
| Protein binding | 95% bound primarily to albumin. |
| Volume of Distribution | 0.2-0.3 L/kg; indicates limited extravascular distribution. |
| Bioavailability | Oral: 70-80%; reduced by food (10-15% decrease). |
| Onset of Action | Intravenous: within 5 minutes; oral: 30-60 minutes. |
| Duration of Action | Intravenous: 4-6 hours; oral: 6-8 hours; prolonged with higher doses or renal impairment. |
10 mg orally twice daily; maximum daily dose: 20 mg.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | GFR 30-89 mL/min: 5 mg twice daily; GFR <30 mL/min: 5 mg once daily. Not studied in hemodialysis. |
| Liver impairment | Child-Pugh A: 5 mg twice daily; Child-Pugh B: 5 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric use. |
| Geriatric use | Initiate at 5 mg twice daily; titrate carefully due to increased risk of hypotension and renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PAREMYD (PAREMYD).
| Breastfeeding | Following ophthalmic administration, both tropicamide and phenylephrine are absorbed in small amounts. Tropicamide has a plasma half-life of 1-2 hours; phenylephrine has a short half-life (~2-3 hours). The likelihood of significant excretion into breast milk is very low; specific M/P ratios are not available for either drug. American Academy of Pediatrics considers phenylephrine compatible with breastfeeding. Tropicamide is not listed but is generally considered compatible due to minimal systemic levels. Infant exposure is negligible; risk is minimal. |
| Teratogenic Risk | Paremyd (0.25% tropicamide and 1% phenylephrine ophthalmic solution) is used for mydriasis and cycloplegia. In pregnancy, systemic absorption is minimal (<5% per dose). Animal studies with tropicamide are limited; no teratogenic effects were noted at clinically relevant doses. Phenylephrine is a vasoconstrictor; high systemic doses may reduce uterine blood flow, but ophthalmic use is unlikely to cause harm. First trimester: Theoretical risk of fetal hypoxia from phenylephrine-induced vasoconstriction is low. Second and third trimesters: No specific risks. Overall, ophthalmic use is considered low risk in all trimesters when used as directed. |
■ FDA Black Box Warning
Warning: May cause a drug-induced lupus-like syndrome (positive antinuclear antibody [ANA] test and symptoms such as arthralgias, myalgias, rash, fever). Discontinue if symptoms develop. Not recommended in patients with rapid acetylator phenotype due to increased risk.
| Serious Effects |
Hypersensitivity to hydralazine or any component; coronary artery disease (relative); dissecting aortic aneurysm; mitral valve rheumatic heart disease (relative); acute myocardial infarction (relative).
| Precautions | Hypotension, tachycardia, myocardial ischemia (use with caution in coronary artery disease), drug-induced lupus (monitor ANA titers), peripheral neuritis (may require pyridoxine), hematologic effects (neutropenia, agranulocytosis), and hypersensitivity reactions. |
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| Fetal Monitoring | No specific maternal or fetal monitoring is required beyond standard prenatal care. If used frequently or in high doses, maternal blood pressure monitoring may be considered due to phenylephrine's vasopressor effects. Monitor for maternal tachycardia, hypertension, or signs of systemic absorption (e.g., blurred vision, photophobia). Fetal heart rate monitoring is not necessary for routine ophthalmic use. |
| Fertility Effects | No known effects on fertility from ophthalmic tropicamide or phenylephrine. Systemic absorption is minimal. No studies have shown impaired male or female fertility in animal or human data. |