CIN-QUIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CIN-QUIN (CIN-QUIN).

How it works

Cin-Quin (quinidine) is a class Ia antiarrhythmic agent that blocks sodium channels, prolonging the effective refractory period and slowing conduction velocity. It also has anticholinergic and alpha-adrenergic blocking properties.

What the body does with it

Metabolism	Metabolized primarily by CYP3A4 to active metabolites (3-hydroxyquinidine and quinidine-N-oxide).
Excretion	Primarily hepatic metabolism; renal excretion of unchanged drug <20%. Biliary/fecal excretion accounts for ~30% of total clearance.
Half-life	Terminal elimination half-life is approximately 4-5 hours in healthy volunteers; prolonged to 8-12 hours in severe malaria or hepatic impairment.
Protein binding	Approximately 70-80% bound, primarily to alpha-1-acid glycoprotein and, to a lesser extent, albumin.
Volume of Distribution	Apparent volume of distribution (Vd) is 1.5-2.5 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral bioavailability is approximately 80% in healthy subjects; may be reduced in patients with malaria due to impaired absorption.
Onset of Action	Intravenous: 15-30 minutes; oral: 1-3 hours.
Duration of Action	Clinical effect persists for 6-8 hours after intravenous dose; oral administration provides coverage for 8-12 hours.

Classification & Brands

Dosing & administration

Quinine sulfate 648 mg (two 324 mg capsules) orally every 8 hours for 7 days, in combination with doxycycline, tetracycline, or clindamycin.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (GFR <10 mL/min), reduce dose by one-third to one-half (e.g., 324 mg every 8 hours) and monitor for toxicity.
Liver impairment	No specific guidelines for Child-Pugh classification; use with caution in severe hepatic impairment (Child-Pugh C) and consider dose reduction by 50% based on clinical response and monitoring of serum levels.
Pediatric use	For malaria: quinine sulfate 10 mg/kg (base) orally every 8 hours for 7 days (maximum 650 mg/dose) in combination with a second agent.
Geriatric use	No specific dose adjustments recommended, but start at lower end of dosing range (e.g., 324 mg every 8 hours) due to age-related renal function decline and increased risk of QT prolongation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CIN-QUIN (CIN-QUIN).

Breastfeeding	Quinine is excreted into breast milk in small amounts. M/P ratio approximately 0.2-0.5. Limited data suggest low risk to infant; however, monitor for signs of cinchonism (e.g., fever, rash, restlessness).
Teratogenic Risk	CIN-QUIN (quinine) is contraindicated in pregnancy due to teratogenicity. First trimester: risk of congenital malformations (e.g., auditory nerve hypoplasia, limb defects). Second and third trimesters: may cause fetal hypoxia and hypoglycemia; avoid use for malaria prophylaxis. Only in severe falciparum malaria when no alternative exists.

Warnings & precautions

■ FDA Black Box Warning

Quinidine has been associated with thrombocytopenic purpura and may exacerbate arrhythmias (proarrhythmia). It should be used with caution in patients with severe heart disease or preexisting arrhythmias.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to quinidine or cinchona alkaloids","Complete AV block without pacemaker","Myasthenia gravis","Digitalis toxicity","History of drug-induced torsades de pointes or QT prolongation"]

Clinical Precautions

Precautions

["May cause QT prolongation and torsades de pointes, especially in patients with hypokalemia, hypomagnesemia, or bradycardia","Cinchonism (tinnitus, hearing loss, blurred vision, nausea) may occur at high doses","Hepatic toxicity and hypersensitivity reactions (including thrombocytopenia)","Monitor serum potassium and magnesium levels","Avoid use with other drugs that prolong QT interval"]

Clinical Tips & Counseling

Drug interactions

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CIN-QUIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CIN-QUIN (CIN-QUIN).

How it works

What the body does with it

Metabolism	Metabolized primarily by CYP3A4 to active metabolites (3-hydroxyquinidine and quinidine-N-oxide).
Excretion	Primarily hepatic metabolism; renal excretion of unchanged drug <20%. Biliary/fecal excretion accounts for ~30% of total clearance.
Half-life	Terminal elimination half-life is approximately 4-5 hours in healthy volunteers; prolonged to 8-12 hours in severe malaria or hepatic impairment.
Protein binding	Approximately 70-80% bound, primarily to alpha-1-acid glycoprotein and, to a lesser extent, albumin.
Volume of Distribution	Apparent volume of distribution (Vd) is 1.5-2.5 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral bioavailability is approximately 80% in healthy subjects; may be reduced in patients with malaria due to impaired absorption.
Onset of Action	Intravenous: 15-30 minutes; oral: 1-3 hours.
Duration of Action	Clinical effect persists for 6-8 hours after intravenous dose; oral administration provides coverage for 8-12 hours.

Classification & Brands

Dosing & administration

Quinine sulfate 648 mg (two 324 mg capsules) orally every 8 hours for 7 days, in combination with doxycycline, tetracycline, or clindamycin.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (GFR <10 mL/min), reduce dose by one-third to one-half (e.g., 324 mg every 8 hours) and monitor for toxicity.
Liver impairment	No specific guidelines for Child-Pugh classification; use with caution in severe hepatic impairment (Child-Pugh C) and consider dose reduction by 50% based on clinical response and monitoring of serum levels.
Pediatric use	For malaria: quinine sulfate 10 mg/kg (base) orally every 8 hours for 7 days (maximum 650 mg/dose) in combination with a second agent.
Geriatric use	No specific dose adjustments recommended, but start at lower end of dosing range (e.g., 324 mg every 8 hours) due to age-related renal function decline and increased risk of QT prolongation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CIN-QUIN (CIN-QUIN).

Breastfeeding	Quinine is excreted into breast milk in small amounts. M/P ratio approximately 0.2-0.5. Limited data suggest low risk to infant; however, monitor for signs of cinchonism (e.g., fever, rash, restlessness).
Teratogenic Risk	CIN-QUIN (quinine) is contraindicated in pregnancy due to teratogenicity. First trimester: risk of congenital malformations (e.g., auditory nerve hypoplasia, limb defects). Second and third trimesters: may cause fetal hypoxia and hypoglycemia; avoid use for malaria prophylaxis. Only in severe falciparum malaria when no alternative exists.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to quinidine or cinchona alkaloids","Complete AV block without pacemaker","Myasthenia gravis","Digitalis toxicity","History of drug-induced torsades de pointes or QT prolongation"]