Quinine Tablets & Injections - Uses, Dose, Side effects

Quinine is an anti-parasitic medicine that is used to treat malaria and babesiosis. It is derived from the bark of a tree called cinchona.

Quinine Uses:

  • Treatment of uncomplicated malaria due to Plasmodium falciparum:

    • Along with other antimalarial medications, it is used to treat mild cases of P. falciparum malaria that is resistant to chloroquine.
  • Off-label Use in adults:

    • Babesiosis
    • Treatment for Plasmodium vivax-caused, simple malaria.

Quinine Dose in Adults

Note:

  • One Qualaquin capsule has 324 mg of quinine sulphate, which is equivalent to 269 mg of base, while Canadian products have either 300 mg of quinine sulphate, which is equivalent to 250 mg of base, or 200 mg of quinine sulphate, which is equivalent to 167 mg of base.

Quinine for the treatment of uncomplicated chloroquine-resistant P. falciparum Malaria:

  • CDC guidelines:

    • In conjunction with doxycycline, tetracycline, or clindamycin, 648 mg per mouth every eight hours (in pregnancy).

Note:

Quinine is given for 3 days in other parts of the world but for infection in Southeast Asia, it is prescribed for one week. Combination therapy is given for one week irrespective of the region.

  • Canadian product:

    • Every eight hours for three to seven days, taking 600 mg orally, combination therapy

Quinine for treating uncomplicated chloroquine-resistant P. vivax Malaria:

  • In conjunction with doxycycline or tetracycline + primaquine, 648 mg per mouth every eight hours.

Quinine for the treatment of Babesiosis (off-label):

  • Taking 650 mg of clindamycin orally every 6 to 8 hours for at least 7 to 10 days.
  • Six-weeks therapy is advised for relapsing infection.

Note:

  • Two capsules (324 mg each, or 648 mg total) of the US-produced quinine sulphate should be used for an adult dose.

Quinine dose in children:

Quinine dose in the treatment of Malaria:

  • Uncomplicated chloroquine-resistant falciparum malaria:

    • Depending on the area, 10 mg/kg per oral quinine sulphate every 8 hours is administered for 3 to 7 days.
    • The maximum dose per dose is 650 mg.
    • Depending on the patient's age, combine with tetracycline, doxycycline, or clindamycin.
  • Uncomplicated chloroquine-resistant Vivax malaria:

    • Depending on the area, 10 mg/kg per oral quinine sulphate every 8 hours for 3 to 7 days
    • The maximum dose per dose is 650 mg.
    • Depending on age, combine with primaquine, tetracycline, or doxycycline.
  • Severe malaria:

    • Once the parasite density is less than 1% and the patient is able to accept oral drugs, oral tablets or solutions can be given after intravenous quinidine, along with an antibiotic regimen.

Quinine for the treatment of Babesiosis:

  • Children and Adolescents:

    • 10 mg/kg per oral  quinine sulfate every 8 hours for 7 to 10 days
    • The maximum dose is 650 mg/dose
    • use in combination with clindamycin as a first-line treatment option.

Quinine dose in pregnancy and lactation: C

  • It can be given during pregnancy.
  • Although the drug can cross the human placental boundary, the therapeutic doses for malaria do not increase the risk of adverse pregnancy outcomes.

Use during breastfeeding:

  • It is found in breastmilk.
  • According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks and benefits to the infant as well as the benefits to the mother.
  • Monitoring is necessary for hemolysis and jaundice especially in children younger than 1 month.
  • Infants with G6PD deficiency should not breastfeed during maternal therapy.

Dose adjustment in renal disease:

  • Mild or moderate impairment:

    • The manufacturer's labelling does not mention dosage modifications.
  • Severe chronic impairment:

    •  US labeling:

      • Patients that are not dialyzed: 648 mg at first, then 324 mg every 12 hours.
    • Canadian product:

      • Initial dose: For seven days, take 600 mg, then 300 mg every 12 hours.
  • Alternative recommendations (Aronoff 2007):

Note: Dosage adjustments are not recommended in cases of severe malaria

    • Glomerular filtration rate >50 mL/minute:

      • No dosage change is required.
    • Glomerular filtration rate 10 to 50 mL/minute:

      • Administer every 8 to 12 hours
    • Glomerular filtration rate <10 mL/minute:

      • Administer each day of the week
    • Intermittent hemodialysis:

      • Dosage following a dialysis session.

Note: 6.5% of the body's waste was cleared within an hour of hemodialysis.

 

  • Peritoneal dialysis:

    • Dose according to GFR 10 mL/minute
  • CRRT:

    • 10 to 50 mL/minute depending on GFR

Dose adjustment in liver disease:

  • Mild to moderate impairment (Child-Pugh classes A and B):

    • No dosage modification is necessary; 
  • Severe impairment (Child-Pugh class C):

    • Avoid use.

Side effects of Quinine:

  • Cardiovascular:

    • Appearance Of U Waves On ECG
    • Atrial Fibrillation
    • Atrioventricular Block
    • Bradycardia
    • Cardiac Arrhythmia
    • Chest Pain
    • Flushing
    • Hypersensitivity Angiitis
    • Hypotension
    • Nodal Rhythm Disorder (Nodal Escape Beats)
    • Orthostatic Hypotension
    • Palpitations
    • Prolonged QT Interval On ECG
    • Syncope
    • Tachycardia
    • Torsades De Pointes
    • Unifocal Premature Ventricular Contractions
    • Vasodilation
    • Ventricular Fibrillation
    • Ventricular Tachycardia
  • Central Nervous System:

    • Altered Mental Status
    • Aphasia
    • Ataxia
    • Chills
    • Coma
    • Confusion
    • Disorientation
    • Dizziness
    • Dystonic Reaction
    • Headache
    • Restlessness
    • Seizure
    • Vertigo
  • Dermatologic:

    • Allergic Contact Dermatitis
    • Bullous Dermatitis
    • Diaphoresis
    • Exfoliative Dermatitis
    • Erythema Multiforme
    • Pruritus
    • Skin Necrosis (Acral)
    • Skin Photosensitivity
    • Skin Rash (Papular Rash
    • Scarlatiniform Rash
    • Urticaria)
    • Stevens-Johnson Syndrome
    • Toxic Epidermal Necrolysis
  • Endocrine & Metabolic:

    • Hypoglycemia
  • Gastrointestinal:

    • Abdominal Pain
    • Anorexia
    • Diarrhea
    • Esophagitis
    • Gastric Irritation
    • Nausea
    • Vomiting
  • Genitourinary:

    • Hemoglobinuria
  • Hematologic & Oncologic:

    • Agranulocytosis
    • Aplastic Anemia
    • Blood Coagulation Disorder
    • Bruise
    • Disseminated Intravascular Coagulation
    • Hemolysis (Blackwater Fever)
    • Hemolytic Anemia
    • Hemolytic-Uremic Syndrome
    • Hemorrhage
    • Hypoprothrombinemia
    • Immune Thrombocytopenia (ITP)
    • Leukopenia
    • Neutropenia
    • Pancytopenia
    • Petechia
    • Thrombocytopenia
    • Thrombotic Thrombocytopenic Purpura
  • Hepatic:

    • Abnormal Hepatic Function Tests
    • Granulomatous Hepatitis
    • Hepatitis
    • Jaundice
  • Hypersensitivity:

    • Hypersensitivity Reaction
  • Immunologic:

    • Antibody Development (Lupus Anticoagulant Syndrome)
  • Neuromuscular & Skeletal:

    • Lupus-Like Syndrome
    • Myalgia
    • Tremor
    • Weakness
  • Ophthalmic:

    • Blindness
    • Blurred Vision (With Or Without Scotomata)
    • Diplopia
    • Mydriasis
    • Nocturnal Amblyopia
    • Optic Neuritis
    • Photophobia
    • Vision Color Changes
    • Vision Loss (Sudden)
    • Visual Field Loss
  • Otic:

    • Auditory Impairment
    • Deafness
    • Tinnitus
  • Renal:

    • Acute Interstitial Nephritis
    • Renal Failure
    • Renal Insufficiency
  • Respiratory:

    • Asthma
    • Dyspnea
    • Pulmonary Edema
  • Miscellaneous:

    • Fever

Contraindications to Quinine:

  • Intolerance to quinine or any other ingredient in the formulation
  • Sensitivity to mefloquine or quinidine (cross-sensitivity reported).
  • Myasthenia gravis
  • Optic neuritis
  • Prolonged QT syndrome
  • Idiopathic thrombocytopenic Purpura
  • Hemolytic uremic syndrome [HUS]
  • Thrombocytopenia due to prior quinine usage.

Warnings and precautions

  • Hemolytic anemia

    • Patients with G6PD deficiency can also experience acute hemolytic anemia. Therefore, it is important to keep your eyes open for these symptoms.
  • Hypersensitivity reactions

    • Stopping therapy for severe hypersensitivity reactions, such as Stevens Johnson syndrome, anaphylactic stress, interstitial Nephritis and neutropenia, is a good idea.
  • Hypoglycemia:

    • Due to the quinine-induced insulin production, use can cause severe hypoglycemia.
  • Thrombocytopenia:

    • It is possible to develop immune-mediated fatal thrombocytopenia. This can be reversed by stopping the drug.
    • TTP can also lead to chronic renal failure.
  • Modified cardiac conduction

    • Reports of atrial fibrillation (or flutter), QT-interval prolongation and fatal torsade des pointes, ventricular fibrillation, and QT-interval prolongation have been made.
    • Concurrent use of drugs causing prolonged QT such as Class IA (eg, quinidine, procainamide) or Class III (eg, amiodarone, dofetilide, sotalol) antiarrhythmic agents should be avoided.

Quinine: Drug Interaction

Risk Factor C (Monitor therapy)

Alkalinizing Agents

May raise the level of quinine in the serum.

Androgens

Can make blood glucose lowering medications more effective at lowering blood sugar. Danazol is an exception.

Antidiabetic Agents

Possibly makes hypoglycemia-associated agents more effective.

Antipsychotic Agents (Phenothiazines)

Antipsychotic Agents' serum concentration may rise in response to antimalarial drugs (Phenothiazines).

Aprepitant

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Blood Pressure Lowering Agents

Blood pressure lowering agents' hypotensive effects may be enhanced by herbs (Hypotensive Properties).

Bosentan

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Brentuximab Vedotin

The serum concentration of Brentuximab Vedotin may rise in response to P-glycoprotein/ABCB1 Inhibitors. More specifically, levels of the substance's active monomethyl auristatin E (MMAE) component might rise.

Celiprolol

Celiprolol's serum levels may rise in response to P-glycoprotein/ABCB1 inhibitors.

CYP2D6 Substrates (High risk with Inhibitors)

The serum concentration of CYP2D6 Substrates may rise in response to quinine (High risk with Inhibitors).

CYP3A4 Inducers (Moderate)

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

CYP3A4 Inhibitors (Moderate)

May slow down CYP3A4 substrate metabolism (High risk with Inhibitors).

Deferasirox

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Digoxin

QuiNINE may increase the serum concentration of Digoxin.

Duvelisib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Erdafitinib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Erdafitinib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Erdafitinib

May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.

Everolimus

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus.

Fingolimod

May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Fosaprepitant

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Fosnetupitant

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Herbs (Hypoglycemic Properties

May intensify the hypoglycemic effects of agents associated with hypoglycemia.

Herbs (Hypotensive Properties)

Could intensify the negative or poisonous effects of other herbs (Hypotensive Properties). There could be signs of excessive blood pressure dropping.

Hypoglycemia-Associated Agents

May increase other hypoglycemia-associated agents' hypoglycemic effects.

Larotrectinib

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Larotrectinib

P-glycoprotein/ABCB1 Inhibitors may raise larotrectinib's serum levels.

Local Anesthetics

The harmful or toxic effects of local anaesthetics may be increased by methemoglobinemia associated agents. In particular, there may be an elevated risk for methemoglobinemia.

Maitake

May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.

Monoamine Oxidase Inhibitors

May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.

Naldemedine

The serum concentration of Naldemedine may rise in response to P-glycoprotein/ABCB1 Inhibitors.

Naloxegol

The quantity of Naloxegol in the serum may rise in response to P-glycoprotein/ABCB1 inhibitors.

Netupitant

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Nevirapine

May lower the level of quinine in the serum.

Nitric Oxide

May intensify the harmful/toxic effects of agents associated with methemoglobinemia. Combinations of these medications may make substantial methemoglobinemia more likely. When nitric oxide is administered along with other medications known to cause the development of methemoglobinemia, patients should be watched closely for symptoms (such as hypoxia and cyanosis). Do not use lidocaine or prilocaine.

Palbociclib

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Pegvisomant

May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.

P-glycoprotein/ABCB1 Inhibitors

May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).

P-glycoprotein/ABCB1 Substrates

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide.

Prilocaine

The harmful or toxic effects of Prilocaine may be increased by methemoglobinemia associated agents. Combinations of these medications may make substantial methemoglobinemia more likely. Monitoring patients for methemoglobinemia symptoms (such as hypoxia and cyanosis) is necessary when prilocaine is used with other medications that can cause methemoglobinemia in patients. When giving these medicines to newborns, avoid using lidocaine or prilocaine.

Prothionamide

Can make blood glucose lowering medications more effective at lowering blood sugar.

Prucalopride

P-glycoprotein/ABCB1 Prucalopride's serum levels may rise in the presence of inhibitors.

QT-prolonging Agents (Indeterminate Risk - Avoid)

May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Agents (Indeterminate Risk - Caution)

May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Quinolones

Can make blood glucose lowering medications more effective at lowering blood sugar. Blood Glucose Lowering Agents' therapeutic impact may be lessened by quinolones. In particular, the use of quinolones may result in a loss of blood sugar control if an agent is being used to treat diabetes.

Ranolazine

The serum concentration of ranolazine may rise in response to P-glycoprotein/ABCB1 inhibitors.

Ranolazine

P-glycoprotein/ABCB1 Substrates serum levels can rise.

RifAXIMin

The concentration of RifAXIMin in the serum may rise in response to P-glycoprotein/ABCB1 inhibitors.

Salicylates

Can make blood glucose lowering medications more effective at lowering blood sugar.

Sarilumab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Selective Serotonin Reuptake Inhibitors

Can make blood glucose lowering medications more effective at lowering blood sugar.

Silodosin

The serum concentration of Silodosin may rise in response to P-glycoprotein/ABCB1 Inhibitors.

Siltuximab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Simeprevir

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Sodium Nitrite

Methemoglobinemia Associated Agents might make sodium nitrite more harmful or hazardous. Combinations of these medications may make substantial methemoglobinemia more likely.

Talazoparib

The serum concentration of Talazoparib may rise in response to P-glycoprotein/ABCB1 inhibitors. Management: Separate interaction monographs are written in-depth for each of the above exceptions.

Tegaserod

Tegaserod's serum levels may rise in response to P-glycoprotein/ABCB1 inhibitors.

Tetracycline (Systemic)

May raise the level of quinine in the serum.

Theophylline Derivatives

Theophylline derivatives' serum levels may be elevated by quinine.

Tobacco (Smoked)

May lower the level of quinine in the serum.

Tocilizumab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Vitamin K Antagonists (eg, warfarin)

The anticoagulant impact of vitamin K antagonists may be strengthened by quinine.

Risk Factor D (Consider therapy modification)

Afatinib

P-glycoprotein/ABCB1 Inhibitors may raise the level of Afatinib in the serum. Management: If afatinib is poorly tolerated, reduce the dose by 10 mg. Some non-US labelling advises staying away from combinations wherever possible. If using, give the P-gp inhibitor either right away or right after the afatinib dose.

Amiodarone

QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Amisulpride

QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.

Arsenic Trioxide

QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Arsenic Trioxide. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Astemizole

QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Astemizole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Azithromycin (Systemic)

The QTc-prolonging effect of azithromycin may be enhanced by QT-prolonging agents (Highest Risk) (Systemic). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Bedaquiline

Bedaquiline's ability to prolong QTc may be enhanced by other QT-prolonging substances (highest risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Bepridil

Bepridil's ability to prolong QTc may be strengthened by other QT-prolonging substances (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients who have additional QTc prolongation risk factors.

Betrixaban

The serum concentration of betrixaban may rise in response to P-glycoprotein/ABCB1 inhibitors. Treatment: If betrixaban is used with a P-glycoprotein inhibitor, reduce the adult dose to an initial single dose of 80 mg, followed by a dose of 40 mg once day.

Bilastine

The serum concentration of bilastine may rise in response to P-glycoprotein/ABCB1 inhibitors. Management: When possible, look into alternatives; bilastine should be avoided in patients using p-glycoprotein inhibitors who have moderate to severe renal insufficiency.

CarBAMazepine

May lower the level of quinine in the serum. CarBAMazepine's serum levels may rise in response to quinine.

Chloroquine

QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

ChlorproMAZINE

QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of ChlorproMAZINE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Cimetidine

May increase the serum concentration of QuiNINE.

Cisapride

Cisapride's ability to prolong QTc may be strengthened by other QT-prolonging substances (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Clofazimine

The QTc-prolonging action of clofazimine may be enhanced by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

CloZAPine

The QTc-prolonging action of CloZAPine may be strengthened by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. Patients who have additional risk factors are probably more at risk, such as older age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher medication concentrations.

Colchicine

The serum concentration of colchicine may rise in response to P-glycoprotein/ABCB1 inhibitors. It's possible that colchicine will distribute more widely throughout some tissues, like the brain. Treatment: Patients receiving a p-glycoprotein inhibitor and having compromised renal or hepatic function should not take colchicine. Colchicine dosage should be decreased in patients with normal renal and hepatic function as instructed. For information, see the entire monograph.

CYP3A4 Inducers (Strong)

May speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.

CYP3A4 Inhibitors (Strong)

May slow down CYP3A4 substrate metabolism (High risk with Inhibitors).

Dabigatran Etexilate

The active metabolite(s) of dabigatran etexilate may be present in higher serum quantities when P-glycoprotein/ABCB1 Inhibitors are used. Reduced doses of dabigatran may be required for treatment. Specific recommendations differ significantly depending on the labelling used in the US versus Canada, the type of P-gp inhibitor used, renal function, and the indication for dabigatran treatment. cite the complete monograph or the dabigatran labelling.

Dabrafenib

May lower the level of CYP3A4 substrates in the serum (High risk with Inducers). Management: When possible, look for CYP3A4 substrate substitutes. Monitor the clinical effects of the substrate carefully if concurrent therapy cannot be avoided (particularly therapeutic effects).

Dapsone (Systemic)

Antimalarial drugs could intensify the harmful or hazardous effects of dapsone (Systemic). In particular, the use of antimalarial medications concurrently with dapsone may raise the risk of hemolytic responses. Dapsone (Systemic) may make antimalarial agents more harmful or poisonous. More specifically, using dapsone at the same time as an antimalarial drug may make hemolytic responses more likely. Treatment: Carefully observe patients for any indications or symptoms of hemolytic responses while administering dapsone and antimalarial medications, especially in those who have haemoglobin M, glucose-6-phosphate dehydrogenase (G6PD), 

Dapsone (Topical)

Antimalarial drugs could intensify the harmful or hazardous effects of dapsone (Topical). Particularly, there may be a higher risk of hemolytic responses. Treatment: Apply topical dapsone and antimalarial medications while closely monitoring for hemolytic reactions' signs and symptoms. Patients who lack glucose-6-phosphate dehydrogenase may be especially vulnerable to negative hematologic consequences.

Dasatinib

Dasatinib's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Delamanid

Delamanid's ability to prolong QTc may be enhanced by other QT-prolonging substances (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Doxepin-Containing Products

The QTcprolonging action of products containing doxepin may be enhanced by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. Patients with additional risk factors, such as older age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher medication concentrations, are more likely to experience adverse outcomes.

DOXOrubicin (Conventional)

Inhibitors of P-glycoprotein/ABCB1 may raise DOXOrubicin's serum concentration (Conventional). Treatment: Whenever possible, avoid using P-glycoprotein inhibitors in patients receiving doxorubicin. Pfizer Inc., a U.S. manufacturer, advises against using certain mixtures.

Dronedarone

QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Dronedarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Droperidol

Droperidol's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Edoxaban

The concentration of Edoxaban in the serum may rise in response to P-glycoprotein/ABCB1 inhibitors. Management: For more, see the whole monograph. Patients taking edoxaban for venous thromboembolism in conjunction with specific P-gp inhibitors are advised to take it in lower doses. It is not advised to modify the dosage when using edoxaban for atrial fibrillation.

Encorafenib

Could make QT-prolonging agents' effect on QTc longer (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Enzalutamide

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation.

Escitalopram

Escitalopram's ability to prolong QTc may be enhanced by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. Patients with additional risk factors, such as older age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher medication concentrations, are more likely to experience adverse outcomes.

Flecainide

Flecainide's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Fluconazole

Fluconazole's ability to prolong QTc may be enhanced by other QT-prolonging substances (highest risk). Fluconazole may increase the QTc-prolonging impact of other QT-prolonging drugs (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Fosphenytoin

May lower the level of quinine in the serum.

Gadobenate Dimeglumine

Gadobenate Dimeglumine's ability to prolong QT intervals may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Gemifloxacin

Potentially amplifies the QTc-prolonging effects of other QT-prolonging agents (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Gilteritinib

Could make QT-prolonging agents' effect on QTc longer (Highest Risk). Management: Take into account alternatives to this fusion. If use is required, keep an eye out for arrhythmias and a prolonged QTc interval.

Haloperidol

QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

HMG-CoA Reductase Inhibitors (Statins)

The serum levels of HMG-CoA Reductase Inhibitors may rise when QuiNINE is used (Statins). When taken with quinine, atorvastatin, simvastatin, or lovastatin may be managed by using reduced starting, maintenance, and maximum doses. Exceptions: Red yeast rice, Rosuvastatin, Fluvastatin, Pitavastatin, and Pravastatin.

Inotuzumab Ozogamicin

Inotuzumab ozogamicin may have a greater QTc-prolonging impact when used with QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Levofloxacin-Containing Products (Systemic)

May increase the QTc-prolonging action of other QT-prolonging agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Lofexidine

QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Lorlatinib

ay lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes.

Methadone

Potentially amplifies the QTc-prolonging effects of other QT-prolonging agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Midostaurin

QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

MiFEPRIStone

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: During and two weeks after mifepristone treatment, reduce doses of CYP3A4 substrates and keep an eye out for elevated amounts or toxicity. Fentanyl, pimozide, quinidine, sirolimus, and tacrolimus should all be avoided. Cyclosporine should also be avoided.

Mitotane

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified.

OLANZapine

OLANZapine's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Ondansetron

Ondansetron's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Osimertinib

Osimertinib's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Pentamidine (Systemic)

QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

PHENobarbital

PHENobarbital's serum levels may be elevated by quinine. PHENobarbital may lower the level of quinine in the blood.

Phenytoin

May lower the level of quinine in the serum.

Pilsicainide

Pilsicainide's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Propafenone

May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Class IA Antiarrhythmics (Highest Risk)

May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Class III Antiarrhythmics (Highest Risk)

May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Dronedarone.

QT-prolonging Kinase Inhibitors (Highest Risk)

May enhance the QTc-prolonging effect of QTprolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Miscellaneous Agents (Highest Risk)

May enhance the QTc-prolonging effect of QuiNINE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Arsenic Trioxide; Astemizole; Bedaquiline; Bepridil; ChlorproMAZINE; Cisapride; Delamanid.

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk)

May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Fluconazole; Nilotinib; Ribociclib.

RisperiDONE

QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Sodium Stibogluconate

QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sodium Stibogluconate. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

St John's Wort

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.

Stiripentol

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought to have a narrow therapeutic index. Use of stiripentol with any CYP3A4 substrate necessitates closer observation.

Telithromycin

May intensify QuiNINE's QTc-prolonging effects. The serum concentration of QuiNINE may rise in response to telithromycin. Treatment: If at all feasible, avoid concurrent therapy with quinine and telithromycin due to the risk of higher quinine serum levels and potential cardiac side effects.

Vemurafenib

QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.

Venetoclax

Venetoclax serum levels may rise in response to P-glycoprotein/ABCB1 inhibitors. In patients who need concurrent treatment with P-glycoprotein (P-gp) inhibitors, consider reducing the dose of venetoclax by at least 50%.

Risk Factor X (Avoid combination)

Antacids

May lower the level of quinine in the serum. Calcium carbonate, potassium bicarbonate, and sodium bicarbonate are exceptions.

Antihepaciviral Combination Products

May raise the level of quinine in the serum.

Artemether

Could intensify the negative or hazardous effects of antimalarial drugs. Management: Unless there are no other treatment options available, artemether/lumefantrine (combination product) should not be used with other antimalarials.

Citalopram

Citalopram's ability to prolong QTc may be enhanced by QT-prolonging Agents (Highest Risk).

Clarithromycin

Clarithromycin's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk).

Conivaptan

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Domperidone

The QTc-prolonging action of Domperidone may be strengthened by QT-prolonging Agents (Highest Risk).

Entrectinib

Could make QT-prolonging agents' effect on QTc longer (Highest Risk).

Flupentixol

Flupentixol's ability to prolong QTc may be enhanced by QT-prolonging Agents (Highest Risk).

Fusidic Acid (Systemic)

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Halofantrine

May intensify QuiNINE's QTc-prolonging effects.

Idelalisib

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Lefamulin

Could intensify the QTc-prolonging effects of CYP3A4 substrates. Management: Avoid taking lefamulin pills with CYP3A4 substrates that prolong QT. The prescribing label for lefamulin states that this combination is not recommended.

Lopinavir

May lower the level of quinine in the serum. Lopinavir/ritonavir has been associated with this outcome. It's unknown how much lopinavir and ritonavir individually contributed to this outcome.

Lumefantrine

Antimalarial drugs may intensify Lumefantrine's harmful or toxic effects. Management: Unless there are no other treatment options available, artemether/lumefantrine (combination product) should not be used with other antimalarials.

Mefloquine

Mefloquine's negative/toxic effects could be exacerbated by quinine. Particularly, there may be an increased risk for QTc-prolongation and convulsions. The serum concentration of QuiNINE may rise in response to mefloquine. Management: When possible, avoid taking two medications at the same time and postpone giving mefloquine until at least 12 hours have passed since the last dosage of quinine.

Moxifloxacin (Systemic)

Moxifloxacin's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk) (Systemic).

Neuromuscular-Blocking Agents

The neuromuscular-blocking effects of neuromuscular-blocking agents may be strengthened by quinine.

Nilotinib

The QTc-prolonging action of nilotinib may be strengthened by QT-prolonging agents (Highest Risk).

PAZOPanib

The serum concentration of PAZOPanib may rise in response to P-glycoprotein/ABCB1 inhibitors.

Pimozide

The QTc-prolonging action of pimozide may be strengthened by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Piperaquine

The QTc-prolonging action of piperaquine may be enhanced by QT-prolonging Agents (Highest Risk).

Posaconazole

May raise the serum level of CYP3A4 substrates that prolong QT. The risk of proarrhythmic effects and other comparable toxicities may increase as a result of such increases.

Probucol

Probucol's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk).

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk)

Potentially amplifies the QTc-prolonging effects of other QT-prolonging agents (Highest Risk). The serum concentration of QT-prolonging Miscellaneous Agents may rise in response to QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) (Highest Risk). For example, clarithromycin.

QUEtiapine

The QTc-prolonging effect of quetiapine may be enhanced by QT-prolonging agents (Highest Risk).

Ribociclib

The QTc-prolonging action of ribociclib may be strengthened by QT-prolonging Agents (Highest Risk).

RifAMPin

May lower the level of quinine in the serum.

Ritonavir

May lower the level of quinine in the serum. Lopinavir/ritonavir has been associated with this outcome. It's unknown how much lopinavir and ritonavir individually contributed to this outcome. Ritonavir's serum levels might be raised by quinine. Ritonavir may raise the level of quinine in the blood.

Sparfloxacin

The QTc-prolonging effect of sparfloxacin may be enhanced by QT-prolonging agents (Highest Risk).

Thioridazine

Thioridazine's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk).

Topotecan

The serum concentration of topotecan may rise in response to P-glycoprotein/ABCB1 inhibitors.

VinCRIStine (Liposomal)

The serum concentration of VinCRIStine may rise in response to P-glycoprotein/ABCB1 Inhibitors (Liposomal).

Monitoring parameters:

  • Complete blood count
  • blood glucose
  • LFTs
  • ECG
  • ophthalmologic examination

How to administer Quinine?

  • It should be taken as a whole orally with food.
  • Because of issues with drug absorption, antacids that contain aluminium or magnesium should be avoided.

Mechanism of action of Quinine:

  • It reduces oxygen uptake and interferes with the metabolism of carbohydrates. 
  • It can also be intercalated into DNA, disrupting replication and transcription. It has similar cardiovascular effects to quinidine.

Rapid absorption occurs mostly from the upper small intestine.

Distribution

  • It is 30 to 50% of plasma concentration that gets into the erythrocytes. It is poorly distributed to the CSF, with a concentration of 2% to 7 %.

Protein binding

  • 69% to 92% for subjects in good health. Due to a rise in alpha 1-acid glycoprotein, malaria patients' survival rates range from 78% to 95%.

Metabolism

  • CYP450 enzymes are responsible for forming metabolites. 3-hydroxyquinine is the most active metabolite, but it is less active than the parent compound.

Bioavailability isHealthy subjects are at 76%-88% when it comes to malaria.

Half-life elimination:

  • Children: 3 hours in healthy subjects; 12 hours with malaria
  • Healthy adults: 10 to 13 hours
  • Healthy elderly subjects: 18 hours

Time to reach peak serum concentration:

  • Children: 2 hours in healthy subjects; 4 hours with malaria
  • Adults: 2 to 4 hours in healthy subjects; 1 to 11 hours with malaria

Excretion:

  • 20 percent of the medication is unaltered in urine; acidic urine increases renal excretion by two times.

Quinine Brand Names (International):

  • Qualaquin
  • APO-QuiNINE
  • JAMP-QuiNINE
  • PRO-QuiNINE-200
  • QuiNINE-Odan
  • TEVA-QuiNINE
  • Aethylcarbonis Chinin
  • Albiquin
  • Circonyl
  • Genin
  • Jasoquin
  • Kanaquine
  • Kinin
  • Malaquin
  • Q200
  • Q300
  • Quinate
  • Quinbisu
  • Quinimax
  • Quininga

Quinine Brand Names in Pakistan:

Quinine 300 mg/ml Injection

Gomal Lahore Chemical & Pharmaceutical Works (Pvt) Ltd
Hydroquine Pharmedic (Pvt) Ltd.
Konien Multinational Buisness Link
Malapak Medicraft Pharmaceuticals (Pvt) Ltd.
Q-Phos Caraway Pharmaceuticals
Quinine Lawrence Pharma
Quinine Dihydrochloride Orient Laboratories
Quinine Dihydrochloride Venus Pharma
Zafquin Zafa Pharmaceutical Laboratories (Pvt) Ltd.

 

Quinine 300 mg Tablets

Circonyl Rotex Medica Pakistan (Pvt) Ltd
Mediquin Semos Pharmaceuticals (Pvt) Ltd.
Pmalamed Medicraft Pharmaceuticals (Pvt) Ltd.
Quinine Bi-Sulphate Lahore Chemical & Pharmaceutical Works (Pvt) Ltd