Qualaquin

quinine sulfate

Apo-Quinine, Novo-Quinine, Qualaquin

Pharmacologic class: Cinchona alkaloid

Therapeutic class: Antimalarial

Pregnancy risk category C

Action

Unknown. Thought to interfere with DNA synthesis by increasing pH in intracellular organelles of susceptible parasites.

Availability

Capsules: 324 mg

Indications and dosages

➣ Uncomplicated Plasmodium falciparum malaria

Adults and children age 16 and older: 648 mg (two capsules) P.O. q 8 hours for 7 days

Dosage adjustment

• Severe chronic renal impairment

Contraindications

• Hypersensitivity to drug (including but not limited to thrombocytopenia, idiopathic thrombocytopenia purpura, thrombocytopenic purpura, hemolytic uremic syndrome, blackwater fever), mefloquine, quinidine

• G6PD deficiency

• Optic neuritis

• Tinnitus

• Prolonged QT interval

• Myasthenia gravis

Precautions

Use cautiously in:

• renal or hepatic impairment

• hypoglycemia

• concurrent use of digoxin and drugs known to prolong QT interval, including Class IA antiarrhythmics (such as disopyramide, procainamide, quinidine) and Class III antiarrhythmics (such as amiodarone, dofetilide, sotalol)

• concurrent use of antacids, rifampin, ritonavir, neuromuscular blockers, macrolide anti-infectives, CYP3A4 substrates, including astemizole, cisapride, terfenadine (not available in U.S.), pimozide, halofantrine, quinidine (avoid use)

• pregnant or breastfeeding patients.

• children younger than age 16 (safety and efficacy of capsules not established).

Administration

• Give with or without food.

Adverse reactions

CNS: headache, vertigo, syncope, apprehension, restlessness, excitement, confusion, delirium, dizziness, seizures

CV: angina, vasculitis, cardiac rhythm or conduction disturbances

EENT: diplopia, amblyopia, blurred vision, scotoma, abnormal color perception, photophobia, night blindness, mydriasis, optic atrophy, hearing loss, tinnitus

GI: nausea, vomiting, diarrhea, abdominal cramps, epigastric pain, dysphagia

GU: hemolytic uremic syndrome Hematologic: hemolytic anemia, hypoprothrombinemia, acute hemolysis, thrombocytopenic purpura, agranulocytosis

Hepatic: hepatotoxicity

Metabolic: hypothermia, hypoglycemia

Respiratory: asthma

Skin: rash, pruritus, photosensitivity, flushing, diaphoresis

Other: cinchonism, facial edema, hypersensitivity reactions including fever and hemolytic uremic syndrome

Interactions

Drug-drug. Aminophylline, theophylline: increased quinine mean area under the curve (AUC) and C_max.

Antacids: delayed or decreased quinine absorption

Atorvastatin, other HMG-CoA reductase inhibitors that are CYP3A4 substrates: increased risk of myopathy

Cimetidine: decreased metabolism and increased effects of quinine

Class IA, Class III antiarrhythmics: increased risk of ECG abnormalities, including prolonged QT interval

CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin): decreased quinine plasma concentration and increased carbamazepine, phenobarbital, and phenytoin AUC and C_max

CYP3A4 inducers or inhibitors, CYP3A4 and CYP2D6 substrates: decreased efficacy and increased adverse effects of these drugs

Digoxin: increased digoxin blood level

Other antimalarials including halofantrine, mefloquine: increased risk of seizures, ECG abnormalities, and cardiac arrest

Neuromuscular blockers: increased effects of these drugs, leading to respiratory difficulty

Rifampin: increased metabolism and decreased effects of quinine

Ritonavir: increased quinine mean AUC, C_max, and elimination half-life

Succinylcholine: delayed succinylcholine metabolism

Tetracycline: increased quinine mean plasma concentration

Urinary alkalizers (such as acetazol-amide, sodium bicarbonate): increased quinine blood level and risk of toxicity

Warfarin: increased warfarin effects, increased risk of bleeding

Drug-diagnostic tests. Urinary 17-ketogenic steroids: elevated levels

Patient monitoring

Monitor for signs and symptoms of hypersensitivity reaction, including fever and hemolytic uremic syndrome. Discontinue drug if signs or symptoms of hypersensitivity occur.

• Stay alert for signs and symptoms of cinchonism, including tinnitus, headache, nausea, and visual disturbances.

Assess for bleeding tendency, arrhythmias, and hepatotoxicity.

• Monitor CBC, renal and liver function tests, and quinine and glucose levels.

Patient teaching

• Tell patient he may take with or without food.

Teach patient to recognize and immediately report signs and symptoms of cinchonism, cardiac arrhythmias, nephrotoxicity, and hepatotoxicity.

Instruct patient to report unusual bleeding or bruising.

• Tell female patient to discuss pregnancy or breastfeeding with prescriber before taking drug.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

quiNINE

(kwi-nine) ,

Qualaquin

(trade name)

Classification

Therapeutic: antimalarials

Pregnancy Category: C

Indications

Chloroquine-resistant falciparum malaria (alone or with pyrimethamine and a sulfonamide or with a tetracycline; has also been used with clindamycin and mefloquine depending on origin of illness).Leg cramps (not recommended due to potentially fatal cardiac side effects).

Action

Disrupts metabolism of the erythrocytic phase of Plasmodium falciparum.

Increases the refractory period of skeletal muscle, increases the distribution of calcium within muscle fibers, decreases the excitability of motor end-plate regions, resulting in decreased response to repetitive nerve stimulation and acetylcholine.

Therapeutic effects

Death of P. falciparum.

Pharmacokinetics

Absorption: Rapidly and almost completely (80%) absorbed following oral administration.

Distribution: Varies with condition and patient; does not enter CSF well. Crosses the placenta and enters breast milk.

Protein Binding: >90% in patients with cerebral malaria, pregnant women, and children; 85–90% in patients with uncomplicated malaria; 70% in healthy adults.

Metabolism and Excretion: >80% metabolized by the liver; metabolites have less activity than quinine; metabolites excreted in urine. 20% excreted unchanged in urine. Excretion ↑ in acidic urine.

Half-life: 11 hr (↑ in patients with malaria).

Time/action profile (antimalarial blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3.2–5.9 hr	8 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to quinine, quinidine, or mefloquine;History of previous serious adverse reaction to quinine including thrombotic thrombocytopenic purpura, thrombocytopenia, acute intravascular hemolysis, hemoglobinuria, or hemoglobinemia;QTc prolongation or conditions predisposing to QTc prolongation including hypokalemia and bradycardia;Concurrent use of Class IA or Class III antiarrhythmics, mefloquine, pimozide, or macrolide anti-infectives (↑ risk of arrhythmias);G6PD deficiency;Myasthenia gravis;Optic neuritis;Severe hepatic impairment Obstetric: Use only if potential maternal benefit outweighs fetal risk; consider alternative therapies; Lactation: Discontinue drug or breastfeeding; Geriatric: Avoid if possible (↑ risk of arrhythmias).

Use Cautiously in: Recurrent or interrupted malaria therapy;History of arrhythmias, especially QTc prolongation;Atrial fibrillation/flutter (may cause paradoxical ↑ in ventricular response);Hypoglycemia;History of thrombocytopenic purpura;Mild or moderate hepatic impairment Pediatric: Children <16 yr (safety not established).

Adverse Reactions/Side Effects

Cardiovascular

• torsades de pointes (life-threatening)
• PR interval prolongation
• QT interval prolongation

Gastrointestinal

• abdominal cramps/pain (most frequent)
• diarrhea (most frequent)
• nausea (most frequent)
• vomiting (most frequent)
• hepatotoxicity

Dermatologic

• rash

Endocrinologic

• hypoglycemia (↑ in pregnancy)

Hematologic

• bleeding
• blood dyscrasias
• thrombotic thrombocytopenic pupura
• thrombocytopenia

Miscellaneous

• cinchonism (most frequent)
• hypersensitivity reactions including fever and anaphylaxis (life-threatening)
• hemolytic uremic syndrome (life-threatening)
• stevens-johnson syndrome (life-threatening)

Interactions

Drug-Drug interaction

Concurrent use of Class IA antiarrhythmics (quinidine, procainamide, disopyramide, Class III antiarrhythmics, mefloquine, pimozide, or macrolide anti-infectives ↑ risk of arrhythmias and should be avoided.Antacids containing aluminum or magnesium ↓ absorption; avoid concurrent use.Cimetidine, ketoconazole, ritonavir, tetracycline, theophylline, and erythromycin may ↑ levels; avoid concurrent use with erythromycin or ritonavir.Rifampin and rifabutin may ↓ levels; avoid concurrent use with rifampin.May ↑ effects of neuromuscular blocking agents.May ↑ risk of hemolytic, ototoxic, or neurotoxic reactions when used concurrently with agents sharing these toxicities.Concurrent use with mefloquine ↑ risk of seizures and adverse cardiovascular reactions.Urinary alkalinizers including acetazolamide and sodium bicarbonate may ↑ blood levels.May ↑ levels of carbamazepine, phenobarbital, atorvastatin, simvastatin, lovastatin, desipramine, dextromethorphan, digoxin, and warfarin.Carbamazepine, phenobarbital, and phenytoin may ↓ levels.

Route/Dosage

Oral (Adults) Malaria—648 mg every 8 hr for 7 days.

Renal Impairment

Oral (Adults) Severe chronic renal failure—648 mg initially, then 324 mg every 12 hr for 7 days.

Availability (generic available)

Capsules: 200 mg, 300 mg, 324 mg

Tablets: 324 mg

Nursing implications

Nursing assessment

• Malaria: Assess patient for improvement in signs and symptoms of condition daily during therapy.
• Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome or toxic epidermal necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
• Monitor for thrombocytopenia; usually resolved within a wk of discontinuation, but may cause a fatal hemorrhage if quinine is not discontinued.
• Lab Test Considerations: May cause ↑ urinary 17-ketogenic steroids when metyrapone or Zimmerman method is used.
Plasma quinine levels of >10 mcg/mL may cause tinnitus and impaired hearing.
• Signs of toxicity or cinchonism include tinnitus, headache, nausea, and slightly disturbed vision; usually disappear rapidly upon discontinuing quinine.

Potential Nursing Diagnoses

Risk for infection (Indications)

Implementation

• Do not confuse quinine with quinidine.
• Oral: Administer with or after meals to minimize GI distress. Aluminum-containing antacids will decrease and delay absorption; avoid concurrent use.

Patient/Family Teaching

• Instruct patient to take medication as directed and continue full course of therapy, even if feeling better. Take missed doses as soon as remembered, unless almost time for the next dose. If more than 4 hr has elapsed since missed dose, wait and take the next dose as scheduled. Do not double doses or take more than recommended. Advise patient to read the Patient Information leaflet prior to starting therapy and with each Rx refill.
• Review methods of minimizing exposure to mosquitoes with patients receiving quinine (use insect repellent, wear long-sleeved shirt and long trousers, use screen or netting).
• Quinine may cause visual changes. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• May cause diarrhea, nausea, stomach cramps or pain, vomiting, or ringing in the ears. Advise patient to notify health care professional promptly if these become pronounced.
• Advise patient to stop quinine and notify health care professional of any evidence of allergy (flushing, itching, rash, fever, facial swelling, stomach pain, difficult breathing, ringing in the ears, visual problems) or rash.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

• Improvement in signs and symptoms of malaria. Advise patient to contact health care professional if not feeling better within 1–2 days or if fever returns following therapy.

Qualaquin

(kwŏl′ə-kwĭn)

A trademark for the drug quinine sulfate.