Antimalarial Drugs

Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria, a vector-borne parasitic disease caused by Plasmodium spp., is transmitted via injection of sporozoites or immature forms of the parasite into a person’s bloodstream. Sporozoites then infect the hepatocytes and differentiate into schizonts, which subsequently rupture, and merozoites invade red blood cells. As such, pharmacotherapy for malaria targets exoerythrocytic and erythrocytic forms of schizonts. Collectively, these agents are classified as schizonticides.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Plasmodia Life Cycle and Prophylaxis

Plasmodium life cycle antimalarial drugs

Plasmodium life cycle

Image by Lecturio.

The treatment of malaria is targeted at different stages of the Plasmodium life cycle:

  • Human liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver stage: targeted with tissue schizonticides
  • Human blood stage: targeted with blood schizonticides
  • Gametocyte stage: targeted with gametocides 
  • Human liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver dormant stages: Hypnozoites can form in P. ovale and P. vivax infections and are targeted with primaquine or tafenoquine.

Treatment consists of 3 steps:

  1. Identification of the infecting Plasmodium species
    • P. falciparum is the most severe; can cause anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and cerebral malaria
  2. Identification of drug susceptibility of the infecting Plasmodium
    • Determined by geographic origin of infection
  3. Patient’s clinical status
    • Avoid the same drug for treatment if it was used prophylactically

Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria prophylaxis and prevention

  • Centers for Disease Control and Prevention (CDC) prophylactic regimens are based on a traveler’s geographic region.
  • Travelers should consult local guidelines (will vary from country to country and with seasons)
  • Principles of prevention
    • Chloroquine: first choice in areas without resistant P. falciparum
    • Mefloquine: first choice in areas with chloroquine-resistant P. falciparum
    • Doxycycline or Malarone® (atovaquone + proguanil): in areas with multidrug-resistant malaria
    • Primaquine: in terminal prophylaxis of P. vivax and P. ovale

Blood Schizonticides, Tissue Schizonticides, and Gametocides

Blood schizonticides

  • Chloroquine
    • Mechanism of action: prevents polymerization of heme and intracellular heme is toxic to the parasite
    • Mechanism of resistance:
      • Plasmodia develop membrane transporters to eject intracellular heme.
      • P. falciparum develops a transporter for chloroquine itself, coded by the P. falciparum chloroquine transporter (pfcrt) gene.
    • Side effects at low doses:
      • Gastrointestinal (GI) disturbances (nausea, cramping, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea)
      • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin rash
      • Headaches
    • Side effects at high doses:
      • Severe skin reactions
      • Peripheral neuropathies, toxic psychosis, retinal and auditory damage
      • Myocardial depression
      • May precipitate porphyria attacks
  • Quinine
    • Mechanism of action: combines with dsDNA, prevents strand separation, blocks replication and transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription
    • Used in chloroquine-resistant P. falciparum
    • Often combined with doxycycline or clindamycin, used to shorten the duration and limit toxicity
    • Toxicity:
      • Cinchonism (GI distress, headache, vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo, blurred vision, tinnitus)
      • Hemolysis in G6PD deficient patients
      • Blackwater fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever (intravascular hemolysis)
  • Mefloquine
    • Chemically related to quinine
    • Mechanism of action: creates toxic heme particles in food vacuoles
    • First-line agent: taken weekly (4 weeks before and 1 week after)
    • Toxicity:
      • GI distress, skin rash, headache, dizziness
      • Nightmares
      • May cause cardiac conduction defects and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures at high doses

Tissue schizonticides

  • Primaquine  
    • Tissue schizonticide and gametocide
    • Used in conjunction with a blood schizonticide
    • Mechanism of action: forms quinoline-quinone metabolites that act as oxidants
    • Eliminates dormant liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver stages (hypnozoites) of P. vivax and P. ovale
    • Toxicity:
      • GI distress, headaches
      • Methemoglobinemia Methemoglobinemia Methemoglobinemia is a condition characterized by elevated levels of methemoglobin in the blood. Methemoglobin is the oxidized form of hemoglobin, where the heme iron has been converted from the usual ferrous (Fe2+) to the ferric (Fe3+) form. The Fe3+ form of iron cannot bind O2, and, thus, leads to tissue hypoxia. Methemoglobinemia, toxicity in G6PD-deficient patients (hemolysis)
      • Contraindicated in pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care

Gametocides

  • Kill sexual stages and prevent transmission to mosquitoes

Gametocidal + schizonticidal:

  • Quinine: gametocidal against P. vivax and ovale 
  • Primaquine: gametocidal against P. falciparum, malariae, ovale, and vivax

Artemisinins and Antifolate Drugs

Artemisinins

  • Blood schizonticides
  • Not used as monotherapy to prevent resistance
  • Only drugs effective against quinine-resistant strains
  • Mechanism of action: accumulate in protozoan food vacuoles, and once metabolized, release toxic free radicals
    • Rare adverse effects of nausea, vomiting, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • No increase in congenital problems or stillbirths in women taking these drugs
  • Short half-lives and not used for malaria prophylaxis
  • Artesunate IV: treatment of severe malaria
  • Artemether-lumefantrine: CDC recommended for uncomplicated malaria treatment in adults and children weighing ≥ 5kg
    • Not to be used in patients on mefloquine prophylaxis  
  • Halofantrine: Active against all 4 plasmodium malarial species
    • Not available in the United States
    • Not recommended by the CDC due to adverse cardiac events
    • Contraindicated in pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • Dihydroartemisinin-piperaquine: not available in the United States and not recommended by the CDC due to widespread resistance

Antifolate drugs

  • Prophylaxis and treatment for multidrug-resistant P. falciparum 
  • Mechanism of action: antimetabolites, block folic acid synthesis
  • Proguanil
    • Inhibits protozoan dihydrofolate reductase (DHFR)
    • Used in combination with atovaquone
  • Pyrimethamine
    • Inhibits DHFR
    • Combination with sulfadoxine (Fansidar®) inhibits both dihydrofolate reductase and dihydropteroate synthase 
    • Not used in the United States
  • Sulfonamides
    • Mechanism of action: inhibit dihydropteroate synthase
    • Adverse reactions: skin rashes Rashes Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Generalized and Localized Rashes, GI upset, hemolysis, kidney damage
    • Sulfadoxine-pyrimethamine: not used in the United States
    • Dapsone: rarely used
  • May combine pyrimethamine and sulfadoxine: synergistic effects through a sequential blockade
  • Toxicity:
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin rash, GI distress
    • Contraindicated in pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care

Erythrocides and Miscellaneous Drugs

Erythrocides

  • Atovaquone
    • Malarone® (atovaquone + proguanil)
    • Used as treatment and as once-daily prophylaxis
    • Is an alternative treatment for P. jiroveci infection
    • Mechanism of action: disrupt mitochondrial electron transport
    • Toxicity:
      • Abdominal pains
      • GI effects
  • Halofantrine
    • Active against erythrocytic forms of all 4 malarial organisms
    • Not used as a chemoprophylactic agent
    • High potential for cardiotoxicity: prolonged QT interval
    • Embryotoxic: contraindicated in pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care

Miscellaneous drugs

  • Doxycycline
    • Used for chemoprophylaxis for travelers
    • Unknown mechanism
  • Amodiaquine
    • Inexpensive
    • Used extensively in the developing world
    • Used in fixed dosing with artesunate
    • Toxicity:
      • Agranulocytosis and aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia

Adverse Effects

Drug Adverse effects
Artemether-lumefantrine (Coartem®) Headache, dizziness, anorexia, nausea/vomiting, weakness, arthralgia, myalgia
Artesunate Headache, dizziness, anorexia, nausea/vomiting
Atovaquone-proguanil (Malarone®) Abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, nausea/vomiting, headache, cough in children
Chloroquine
  • GI upset, headache, exacerbation of psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis, retinal toxicity, visual impairment
  • Blue-gray skin pigmentation with long-term use
  • Cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Overview of Cardiomyopathies and QT prolongation have been seen with long-term therapy
Hydroxychloroquine GI upset, headache, rash, visual changes
Doxycycline Photosensitivity, GI upset (mitigated by taking with food), permanent tooth discoloration in children < 8 years
Mefloquine
  • GI upset, skin rash, headache, dizziness
  • Psychiatric effects: nightmares, anxiety, depression
  • Cardiac conduction defects
  • Seizures at high doses
Primaquine GI upset, headaches, methemoglobinemia, hemolysis (due to G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency)
Quinidine
  • Hemolysis ( G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency)
  • Cinchonism (syndrome of nausea, vomiting, tinnitus, and vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo)
  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia (quinine-induced insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin release)
  • Blackwater fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: uncommon anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview of massive hemolysis with “Coca-Cola”-colored urine
Tafenoquine
  • Dizziness, nausea/vomiting, headache
  • Psychiatric effects are rarely seen (in ≤ 3% of patients): somnolence, anxiety, abnormal dreams, depression

Overview

Drug Classification Mechanism of action Usage Contraindications
Artemether-lumefantrine (Coartem®)
  • Blood schizonticide
  • Artemisinin-aryl alcohol combination
Metabolized in plasmodial food vacuole to toxic free radicals
  • Treatment of uncomplicated P. falciparum malaria in patients weighing ≥ 5 kg
  • Treatment of severe malaria after the administration of IV artesunate
  • Strong CYP3A4 inducers
  • Known hypersensitivity to artemisinins
Artesunate
  • Blood schizonticide
  • Artemisinin
Metabolized in plasmodial food vacuole to toxic free radicals
  • First-line treatment for severe malaria in the United Sates (CDC recommended, not FDA approved)
  • 3-day treatment of 4 equal IV doses of 2.4 mg/kg
  • Followed by one of the following PO:
    1. Artemether-lumefantrine
    2. Atovaquone-proguanil
    3. Doxycycline
    4. Clindamycin
    5. Mefloquine (if no other options)
Known hypersensitivity to artemisinins
Atovaquone-proguanil (Malarone®)
  • Blood schizonticide
  • Tissue schizonticide
  • Quinone- folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 antagonist
  • Atovaquone inhibits the plasmodial electron transport chain Electron transport chain The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC)
  • Proguanil inhibits DHFR and blocks plasmodial DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure synthesis
  • Prophylaxis in all areas
  • Taken with milk or fatty meal to aid absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
Severe renal impairment (CrCl < 30 mL/minute)
Chloroquine
  • Blood schizonticide
  • 4-Aminoquinoline
Enters the food vacuoles of Plasmodia and disrupts heme polymerization Prophylaxis in areas with chloroquine-sensitive malaria
  • Retinal or visual changes
  • Caution in patients with porphyrias Porphyrias Porphyrias are a group of metabolic disorders caused by a disturbance in the synthesis of heme. In most cases, porphyria is caused by a hereditary enzyme defect. The disease patterns differ depending on the affected enzyme, and the variants of porphyria can be clinically differentiated between acute and nonacute forms. Porphyrias, psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, pre-existing hearing impairment
Hydroxychloroquine Blood schizonticide Known hypersensitivity to 4-aminoquinolone derivatives
Doxycycline
  • Tetracycline
  • Blood schizonticide
Inhibits protein synthesis in the plasmodial apicoplast
  • Prophylaxis in all areas
  • Treatment with quinine
  • Children < 8 years old
  • Pregnancy or breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
Mefloquine
  • Blood schizonticide
  • Quinoline methanol
Enters the food vacuoles of Plasmodia and disrupts heme polymerization Prophylaxis in areas with chloroquine-sensitive malaria or chloroquine-resistant areas
  • History of seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Psychiatric disorders
Primaquine
  • Tissue schizonticide, including hypnozoites
  • 8-Aminoquinoline
  • Forms quinoline-quinone metabolites that act as oxidants
  • Gametocidal against P. falciparum, malariae, ovale, and vivax
Prophylaxis in P. vivax predominant areas
  • Treatment for presumptive antirelapse therapy of P. ovale and P. vivax
  • In conjunction with chloroquine (blood schizonticide)
  • Taken for 14 days after departing malaria area
  • G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency
  • Lupus erythematosus
  • Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis
  • Pregnancy and breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
Quinidine IV
  • Blood schizonticide
  • Quinoline methanol
Interferes with heme polymerization Discontinued in the United States
Quinine
  • Blood schizonticide
  • Quinoline methanol
  • Interferes with heme polymerization
  • Gametocidal against P. vivax and P. ovale
  • Treatment of uncomplicated chloroquine-sensitive malaria
  • Quinine sulfate oral PLUS either:
    • Doxycycline
    • Tetracycline
    • Clindamycin (preferred in first trimester of pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care)
  • Prolonged QT interval
  • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
  • Optic neuritis
Tafenoquine
  • Tissue and blood schizonticide, including hypnozoites
  • Gametocide
  • 8-Aminoquinoline derivative
Interferes with heme polymerization Prophylaxis in all areas
  • Treatment of presumptive antirelapse therapy of P. ovale and P. vivax
  • Administered as a single dose after departing malaria area
  • G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency
  • Pregnancy and breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
  • Children < 16 years old
  • History of or active psychotic disorder

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