PHENAZINE-35

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHENAZINE-35 (PHENAZINE-35).

How it works

PHENAZINE-35 is a synthetic phenazine derivative that inhibits bacterial DNA synthesis by intercalating into DNA and disrupting topoisomerase IV activity, leading to cell death.

What the body does with it

Metabolism	Primarily metabolized via hepatic CYP3A4 and CYP1A2 isoenzymes; also undergoes conjugation with glucuronic acid.
Excretion	Renal: ~70% (30% unchanged, 40% as metabolites); Biliary/Fecal: ~30%
Half-life	Terminal half-life: 12-18 hours (mean 15 h). Clinically, steady-state achieved in ~3 days, allows once-daily dosing.
Protein binding	98% bound; primarily to albumin and α1-acid glycoprotein
Volume of Distribution	Vd: 7-12 L/kg (mean 10 L/kg); indicates extensive tissue distribution with CNS penetration.
Bioavailability	Oral: 45-55% (due to first-pass metabolism); IM: 75-85%; IV: 100%
Onset of Action	Oral: 30-60 min; IM: 15-30 min; IV: 5-10 min
Duration of Action	Oral: 6-12 h; IM: 8-12 h; IV: 4-6 h. Duration prolonged in hepatic impairment.

Classification & Brands

Dosing & administration

25 mg orally three times daily, titrated to a maximum of 100 mg three times daily.

Dosage form	TABLET
Renal impairment	No specific adjustment required; use with caution in severe renal impairment (GFR <30 mL/min).
Liver impairment	Child-Pugh Class A: no adjustment. Class B: reduce dose by 50%. Class C: avoid use.
Pediatric use	Not recommended for pediatric patients due to lack of safety and efficacy data.
Geriatric use	Initiate at 12.5 mg orally twice daily; titrate slowly due to increased risk of adverse effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PHENAZINE-35 (PHENAZINE-35).

Breastfeeding	Excreted in breast milk (M/P ratio 0.8). Avoid breastfeeding due to risk of infant sedation and apnea; alternative agents preferred if required.
Teratogenic Risk	First trimester: Risk of neural tube defects and congenital heart malformations (OR 1.5-2.0). Second/third trimester: Dose-dependent risk of fetal growth restriction and preterm birth. Avoid after 34 weeks due to premature ductus arteriosus closure.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

WARNING: Increased risk of tendinitis and tendon rupture, especially in patients over 60 years of age, those taking corticosteroids, and those with kidney, heart, or lung transplants.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to phenazine derivatives or any component of the formulation; concomitant use with tizanidine; history of tendinopathy related to fluoroquinolones; pregnancy (category D) and lactation.

Clinical Precautions

Precautions

Use with caution in patients with a history of tendon disorders, renal impairment (dose adjustment required), and myasthenia gravis; may prolong QT interval; avoid excessive sun exposure due to photosensitivity.

Clinical Tips & Counseling

Drug interactions

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PHENAZINE-35

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHENAZINE-35 (PHENAZINE-35).

How it works

PHENAZINE-35 is a synthetic phenazine derivative that inhibits bacterial DNA synthesis by intercalating into DNA and disrupting topoisomerase IV activity, leading to cell death.

What the body does with it

Metabolism	Primarily metabolized via hepatic CYP3A4 and CYP1A2 isoenzymes; also undergoes conjugation with glucuronic acid.
Excretion	Renal: ~70% (30% unchanged, 40% as metabolites); Biliary/Fecal: ~30%
Half-life	Terminal half-life: 12-18 hours (mean 15 h). Clinically, steady-state achieved in ~3 days, allows once-daily dosing.
Protein binding	98% bound; primarily to albumin and α1-acid glycoprotein
Volume of Distribution	Vd: 7-12 L/kg (mean 10 L/kg); indicates extensive tissue distribution with CNS penetration.
Bioavailability	Oral: 45-55% (due to first-pass metabolism); IM: 75-85%; IV: 100%
Onset of Action	Oral: 30-60 min; IM: 15-30 min; IV: 5-10 min
Duration of Action	Oral: 6-12 h; IM: 8-12 h; IV: 4-6 h. Duration prolonged in hepatic impairment.

Classification & Brands

Dosing & administration

25 mg orally three times daily, titrated to a maximum of 100 mg three times daily.

Dosage form	TABLET
Renal impairment	No specific adjustment required; use with caution in severe renal impairment (GFR <30 mL/min).
Liver impairment	Child-Pugh Class A: no adjustment. Class B: reduce dose by 50%. Class C: avoid use.
Pediatric use	Not recommended for pediatric patients due to lack of safety and efficacy data.
Geriatric use	Initiate at 12.5 mg orally twice daily; titrate slowly due to increased risk of adverse effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PHENAZINE-35 (PHENAZINE-35).

Breastfeeding	Excreted in breast milk (M/P ratio 0.8). Avoid breastfeeding due to risk of infant sedation and apnea; alternative agents preferred if required.
Teratogenic Risk	First trimester: Risk of neural tube defects and congenital heart malformations (OR 1.5-2.0). Second/third trimester: Dose-dependent risk of fetal growth restriction and preterm birth. Avoid after 34 weeks due to premature ductus arteriosus closure.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

WARNING: Increased risk of tendinitis and tendon rupture, especially in patients over 60 years of age, those taking corticosteroids, and those with kidney, heart, or lung transplants.