Quinine

Quinine is an antimalarial agent belonging to the pharmacological class of cinchona alkaloid.

The FDA has approved Quinine for treating uncomplicated Malaria caused by the parasite Plasmodium falciparum.

Quinine is rapidly and nearly completely absorbed in the gastrointestinal tract. The body widely distributes it but poorly penetrates CSF. It undergoes extensive metabolism in the liver, primarily by the CYP3A4 isoenzyme, forming 3-hydroxyquinoline and other metabolites. Urine eliminates approximately 20% as an unchanged drug, with increased excretion in acidic urine.

The most common side effects of Quinine include vomiting, headache, and dizziness.

Quinine is available as oral tablets/ capsules, oral suspension and injectable solutions.

The molecule is available in the United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.

Quinine is an antimalarial agent belonging to the pharmacological class of cinchona alkaloid.

Quinine sulfate inhibits the synthesis of proteins and nucleic acids and glycolysis in Plasmodium falciparum, P vivax, P ovale, and P malariae. It acts quickly against these parasites. Binding with hemozoin in infected red blood cells interferes with transcription and DNA replication. It has schizontocidal activity, which affects how the parasites metabolize carbohydrates and take in oxygen. Quinine is effective against different Plasmodium species, but its exact antimalarial action is still unknown.

The time required for Quinine to show its effects is generally within several hours after administration.

The effects of Quinine may last for several hours after administration.

The maximum plasma concentration (Cmax) of Quinine typically occurs within 1-3 hours (Tmax) after administration.

Quinine is available as oral tablets/ capsules, oral and injectable solutions.

Tablets/Capsules: To be swallowed whole with water/liquid. Do not chew, crush or break it.

Oral solutions: Measured using a dosing spoon or cup. Shake the bottle well before use.

Injectable solutions: To be administered slowly via IV infusion.

The physician recommends taking the medication every 8 hours for 7 days. It can be taken with or without food as directed.

Quinine can be used for various health conditions:

Quinine is not approved for any of the following conditions:

Quinine is an effective antimalarial essential for eliminating fever, fighting Plasmodium parasites, and treating malaria symptoms. It works by preventing the growth and replication of the parasites in the bloodstream; it helps the patient recover from this potentially fatal illness.

Quinine is indicated only for the treatment of uncomplicated Plasmodium falciparum malaria or for patients unable to tolerate other antimalarial medications.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Tablets/Capsules: 200mg, 300mg, 324mg, 600mg

Oral Solution: 200 mg/5 mL

Injectable Solution: 60 mg/mL, 100 mg/5 mL, 150mg/ 5 mL, 300 mg/2 mL or 500 mg/mL.

Quinine is available as oral tablets/ capsules, oral and injectable solutions.

Uncomplicated (P falciparum)

q8hr x 7 days of 648 mg PO

resistant to chloroquine (P falciparum)

648 mg PO every 8 hours for 3–7 days while concurrently taking clindamycin, doxycycline, or tetracycline

resistant to chloroquine (P vivax)

648 mg PO every 8 hours for 3-7 days, along with PO primaquine and concurrent doxycycline (or tetracycline).

First, a loading dose of 20 mg/kg (maximum: 1,400 mg) was infused over 4 hours, and maintenance infusions began after 8 hours. This is the quinine dihydrochloride dosage. Max: 700 mg; maintenance: 10 mg/kg 8 hourly infused for 4 hours. The first maintenance infusions can be given immediately after the initial loading dose of 7 mg/kg, which can be handed over for 30 minutes in intensive care units. Use 5-7 mg/kg as the maintenance dose if parenteral therapy is needed for longer than 48 hours. Patients who have taken Quinine or mefloquine within the last 12 hours shouldn't receive a loading dose.

648 mg PO q8hr for 7 days, with concomitant PO or IV clindamycin.

It is advised to avoid tonic water or any quinine sources while on medication to prevent excessive intake. Quinine may interact with certain foods like grapefruit, affecting its metabolism and concentration. Alcohol intensifies side effects and isn't recommended. Stay hydrated by drinking regular water to prevent kidney complications. Be cautious with highly acidic foods to avoid gastric upset. Consume nutritious foods like fresh fruits and vegetables for recovery. If appetite is low, opt for glucose water, fresh fruit juices, and coconut water. Incorporate high-fiber foods like green leafy vegetables and fruits for digestion. Ensure adequate rest for faster healing.

The dietary restriction should be individualized as per patient requirements.

Quinine may be contraindicated in the following conditions: -

The adverse reactions related to Quinine can be categorized as

The clinically relevant drug interactions of Quinine are briefly summarized here.

Halofantrine and other medications known to lengthen the QT interval (such as amiodarone, astemizole, terfenadine, cisapride, moxifloxacin, pimozide, and thioridazine) carry an increased risk of causing ventricular arrhythmia. Mefloquine increases the chance of convulsions. It may enhance the effects of oral hypoglycemic medications, neuromuscular blocking medicines, and anticoagulants. Decreased amantadine renal clearance. Reduced plasma concentrations of rifampicin, phenobarbital, phenytoin, and carbamazepine. Elevated ritonavir plasma levels. It may impede or postpone the absorption of magnesium and/or aluminum antacids. Decreased ciclosporin levels in the plasma. Elevated digoxin plasma levels. Atorvastatin-associated increased risk of myopathy and rhabdomyolysis.

The common side effects of Quinine include: -

Pregnancy Category C (FDA): Use caution if the benefits outweigh the risks.

At doses recommended for treating Malaria, Quinine does not cause uterine contractions. Higher dosages, though, perhaps several times higher than those used in malaria treatments, may stimulate the uterus during pregnancy.

Many published studies evaluate quinine sulfate in pregnant women, but there aren't many well-controlled ones. Over 1,000 quinine exposures during pregnancy were documented compared to the general population, with no increase in teratogenic effects. However, most of these exposures did not happen in the first trimester. As a result, Quinine should only be used if there are more potential advantages than risks to the developing fetus.

It is still imperative to treat Malaria during pregnancy since P. falciparum infections carry more significant risks of morbidity and death. P. falciparum malaria patients who are pregnant have a higher chance of miscarriage, low birth weight, preterm labour, low fetal development, and maternal death. Because Quinine increases insulin secretion, it can cause hypoglycemia, especially in pregnant women.

There are low quantities of Quinine in breastmilk; an infant's consumption of these amounts is unlikely to have any adverse effects. There is no data on the impact of Quinine on breastfed infants or the effects on milk production.

The dosage in milk is far less than what is needed to treat Malaria in a baby.

Use caution in mothers with a newborn deficient in glucose-6-phosphate dehydrogenase (G6PD).

Hemolysis in G6PD-deficient babies has been reported in response to relatively small doses of Quinine in tonic water consumed by nursing mothers.

As per the FDA, the safety and efficacy of Quinine in pediatric patients have yet to be extensively studied or established.

The recommended PO dosage for adults should not exceed 30 mg/kg/day divided TID x 3–7 days.

P falciparum, which is resistant to chloroquine, 30 mg/kg/day PO divided TID x 3–7 days, along with concurrent doxycycline, tetracycline, or clindamycin; dose shouldn't exceed that of an adult PO.

P vivax, a chloroquine-resistant strain, 30 mg/kg/day PO TID for three to seven days, and concurrent PO primaquine and doxycycline Should not exceed the standard adult PO dosage.

25 mg/kg/day PO divided TID for seven days, along with concurrent oral clindamycin

Kidney impairment: The dosage and dosing frequency should be reduced. In case of severe impairment, clearance of Quinine is decreased; 648 mg PO once, then 324 mg PO every 12hr.

Quinine should be used with caution in patients with liver disease. Dose adjustment of Quinine may not be needed in mild to moderate illness.

Not recommended in the patients with severe liver disease.

The physician should be vigilant about the knowledge pertaining to the identification and management of overdosage of Quinine.

Overdosage of Quinine can be associated with severe complications, including visual impairment, cardiac arrhythmias, hypoglycemia, and death.

Overconsumption of Quinine needs to be treated immediately, but there is no known cure or antidote. Consider prompt supportive action, such as monitoring electrolytes, acid-base balance, and cardiac activity. If activated charcoal is given within hours of consumption, it may help reduce absorption in extreme cases. To remove Quinine and handle complications, use invasive techniques such as hemoperfusion or hemodialysis for large overdoses. Monitor for any possible seizures, hypoglycemia, and cardiac arrhythmias. Treat convulsions with intravenous diazepam or anti-arrhythmic drugs. Maintain adequate hydration and correct hypoglycemia if it occurs. Close vital sign monitoring is crucial, emphasizing timely medical intervention to mitigate potential risks from Quinine overdose.

Quinine is mainly used to treat infections that can be fatal and are brought on by Plasmodium falciparum malaria, which is resistant to chloroquine. Quinine has gametocytocidal activity against P. vivax and P. malariae but also works as a blood schizonticide. Due to its weak baseness, it is concentrated in P. falciparum's feeding vacuoles. It is believed to work by preventing heme polymerase from functioning, which permits heme—its deadly substrate—to accumulate. It is more hazardous and less effective than chloroquine as a schizonticidal medication. However, it does have a distinctive function in treating severe falciparum malaria in regions where chloroquine resistance is recognized.

The gastrointestinal tract rapidly and nearly wholly absorbs Quinine. It reaches its peak concentration in the plasma within approximately 1-3 hours.

It extensively spreads throughout the body but struggles to penetrate the cerebrospinal fluid, accounting for about 2-7% of the plasma concentration. Quinine crosses the placenta barrier and transfers into breast milk. Its volume of distribution ranges between 2.5-7.1 L/kg. In healthy patients, approximately 70% of Quinine binds to plasma proteins, while malaria patients exhibit a higher binding capacity of ≥90%.

The liver extensively metabolizes Quinine through oxidative CYP450 pathways, particularly the CYP3A4 isoenzyme. This process forms metabolites like 3-hydroxyquinoline.

Roughly 20% of the drug undergoes elimination via urine, and its excretion rises in acidic urine conditions. The drug has an elimination half-life of about 11 hours in healthy individuals.