Arakoda
Generic: TAFENOQUINE
Basic Information
Manufacturer
60 Degrees Pharmaceuticals, INC.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
299e49d8-470f-4779-a010-4a1ee0e0c6cd
Indications & Usage
1 INDICATIONS AND USAGE ARAKODA is indicated for the prophylaxis of malaria in patients aged 18 years and older.
ARAKODA is an antimalarial indicated for the prophylaxis of malaria in patients aged 18 years and older.
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ARAKODA is an antimalarial indicated for the prophylaxis of malaria in patients aged 18 years and older.
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Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions observed with ARAKODA are discussed in detail in the Warnings and Precautions section: • Hemolytic Anemia [see Warnings and Precautions ( 5.2 )] • Methemoglobinemia [see Warnings and Precautions ( 5.3 )] • Psychiatric Effects [see Warnings and Precautions ( 5.4 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] The most common adverse reactions (incidence ≥1%) were: headache, dizziness, back pain, diarrhea, nausea, vomiting, increased alanine aminotransferase (ALT), motion sickness, insomnia, depression, abnormal dreams, anxiety.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact 60 Degrees Pharmaceuticals at 1-888-834-0225 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of tafenoquine was studied in clinical trials at various doses and regimens in 3,184 subjects.
The recommended ARAKODA regimen was evaluated in 825 subjects in 5 controlled clinical trials (Trials 1, Trial 2, Trial 3, Trial 4 and Trial 5).
The mean duration of exposure to ARAKODA in these five clinical trials was 21 weeks (range 10-29 weeks).
Trial 1, 2 and 4 were conducted in healthy semi-immune volunteers in Ghana or Kenya and were placebo-controlled; a mefloquine arm was included in Trials 2 and 4 as a benchmark.
Trial 3, an active comparator (mefloquine) controlled trial was conducted in healthy soldiers deployed in East Timor (Timor Leste).
A placebo-controlled Trial 5 was conducted in healthy volunteers in the United States and United Kingdom.
The mean age of the subjects included in the five trials was 29 years (range 17 to 69 years); 84% were male.
Adverse Reactions Reported with ARAKODA in Trial 3 and Pooled Trials 1, 2, 4, and 5 Adverse reactions occurring in ≥1% of subjects in the ARAKODA group in the placebo-controlled pooled Trials 1, 2, 3, and 4 are presented in Table 3 .
Table 3: Selected Adverse Reactions Occurring in ≥1% of Subjects Receiving ARAKODA in Pooled Trials 1, 2, 4, and 5 (Non-Deployed Subjects) Adverse Reaction ARAKODA 1 (n=333) % Placebo (n=295) % Mefloquine 2 (n=147) % 1 ARAKODA was administered as 200 mg daily for 3 days, then 200 mg weekly 2 Mefloquine was administered as 250 mg daily for 3 days, then 250 mg weekly 3 Includes headache, sinus headache, migraine and tension headache.
4 Includes dizziness and dizziness postural 5 Includes abnormal dreams, insomnia, nightmares, sleep disorder, and somnambulism.
Nervous system Disorders 35 34 47 Headache 3 32 32 44 Dizziness 4 5 3 10 Musculoskeletal and connective tissue disorders 27 26 37 Back pain 14 9 11 Gastrointestinal disorders 31 33 46 Diarrhea 5 3 1 Nausea 5 2 2 Vomiting 2 2 1 Investigations 8 7 11 Alanine Aminotransferase (ALT) increased/abnormal 4 2 3 Psychiatric disorders 2 1 2 Any sleep symptom 5 1 1 0 Insomnia 1 1 0 Depression/depressed mood 1 0 0 Adverse reactions occurring in ≥1% of subjects in the ARAKODA group in the active-control Trial 3 conducted in military personnel deployed to malaria endemic areas are presented in Table 4 .
Table 4: Selected Adverse Reactions Occurring in ≥1% of Subjects Receiving ARAKODA in Trial 3 (Deployed Subjects) Adverse Reaction ARAKODA 1 (n=492) % Mefloquine 2 (n=162) % 1 ARAKODA was administered as 200 mg daily for 3 days, then 200 mg weekly 2 Mefloquine was administered as 250 mg daily for 3 days, then 250 mg weekly 3 Includes headache, sinus headache, migraine and tension headache.
4 Includes dizziness and dizziness postural 5 Includes motion sickness, vertigo and vertigo positional.
6 Includes abnormal dreams, insomnia, nightmares, sleep disorder, and somnambulism.
7 Includes abnormal dreams, nightmares 8 Includes anxiety disorder, panic attack and stress.
Nervous system Disorders 22 27 Headache 3 15 19 Dizziness 4 1 1 Ear and labyrinth Disorders 7 11 Motion sicknesss 5 5 6 Musculoskeletal and connective tissue disorders 29 30 Back pain 14 15 Gastrointestinal disorders 36 41 Diarrhea 18 20 Nausea 7 9 Vomiting 5 6 Psychiatric disorders 5 4 Any sleep symptom 6 4 4 Insomnia 2 1 Abnormal dreams 7 2 2 Anxiety 8 1 0 Clinically Significant Adverse Reactions in Trials 1 to 5 (Overall Safety Population) Clinically significant adverse reactions with ARAKODA (200 mg daily for 3 days, followed by 200 mg weekly) in Trials 1 to 5 (n= 825) are described below: Ocular Adverse Reactions Vortex keratopathy was reported in 21% to 93% of subjects receiving ARAKODA in the trials which included ophthalmic evaluations (Trials 3, 5, and Trial 6 (NCT # 01290601, an active-control trial in patients from Thailand with P.
vivax malaria.
The keratopathy did not result in any apparent functional visual changes and resolved within one year after drug cessation in all patients.
Retinal abnormalities were noted in less than 1% of subjects receiving ARAKODA.
A total of 7 serious ocular adverse reactions (SARs) were reported in ARAKODA-treated subjects in the trials which included ophthalmic evaluations: 5 reports of keratopathy and two reports of retinal disorders.
Laboratory Abnormalities Methemoglobinemia: Asymptomatic methemoglobin elevations were observed in 13% of subjects receiving ARAKODA.
Hemoglobin decrease: Hemoglobin decreases of ≥ 3 g/dL were observed in 2.3% of subjects receiving ARAKODA.
Adverse Reactions Reported in < 1% of Subjects Receiving ARAKODA in Trials 1 to 5 The following selected adverse reactions were reported in subjects receiving ARAKODA in Trials 1 to 5 at a rate of less than 1%.
Blood and lymphatic system disorders: hemolytic anemia, anemia, thrombocytopenia Ear and labyrinth disorders: hyperacusis, Meniere’s disease Eye disorders: night blindness, photophobia, blurred vision, visual acuity reduced, visual impairment, vitreous floaters Hepatobiliary disorders: hyperbilirubinemia, jaundice cholestatic Immune system disorders: hypersensitivity Investigations: blood bilirubin increased, blood creatinine increased, glomerular filtration rate decreased Nervous system disorders: amnesia, coordination abnormal, hyperesthesia, hypoesthesia, somnolence, syncope, tremor, visual field defect Psychiatric disorders: agitation, neurosis Skin and subcutaneous tissue disorders: urticaria.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact 60 Degrees Pharmaceuticals at 1-888-834-0225 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of tafenoquine was studied in clinical trials at various doses and regimens in 3,184 subjects.
The recommended ARAKODA regimen was evaluated in 825 subjects in 5 controlled clinical trials (Trials 1, Trial 2, Trial 3, Trial 4 and Trial 5).
The mean duration of exposure to ARAKODA in these five clinical trials was 21 weeks (range 10-29 weeks).
Trial 1, 2 and 4 were conducted in healthy semi-immune volunteers in Ghana or Kenya and were placebo-controlled; a mefloquine arm was included in Trials 2 and 4 as a benchmark.
Trial 3, an active comparator (mefloquine) controlled trial was conducted in healthy soldiers deployed in East Timor (Timor Leste).
A placebo-controlled Trial 5 was conducted in healthy volunteers in the United States and United Kingdom.
The mean age of the subjects included in the five trials was 29 years (range 17 to 69 years); 84% were male.
Adverse Reactions Reported with ARAKODA in Trial 3 and Pooled Trials 1, 2, 4, and 5 Adverse reactions occurring in ≥1% of subjects in the ARAKODA group in the placebo-controlled pooled Trials 1, 2, 3, and 4 are presented in Table 3 .
Table 3: Selected Adverse Reactions Occurring in ≥1% of Subjects Receiving ARAKODA in Pooled Trials 1, 2, 4, and 5 (Non-Deployed Subjects) Adverse Reaction ARAKODA 1 (n=333) % Placebo (n=295) % Mefloquine 2 (n=147) % 1 ARAKODA was administered as 200 mg daily for 3 days, then 200 mg weekly 2 Mefloquine was administered as 250 mg daily for 3 days, then 250 mg weekly 3 Includes headache, sinus headache, migraine and tension headache.
4 Includes dizziness and dizziness postural 5 Includes abnormal dreams, insomnia, nightmares, sleep disorder, and somnambulism.
Nervous system Disorders 35 34 47 Headache 3 32 32 44 Dizziness 4 5 3 10 Musculoskeletal and connective tissue disorders 27 26 37 Back pain 14 9 11 Gastrointestinal disorders 31 33 46 Diarrhea 5 3 1 Nausea 5 2 2 Vomiting 2 2 1 Investigations 8 7 11 Alanine Aminotransferase (ALT) increased/abnormal 4 2 3 Psychiatric disorders 2 1 2 Any sleep symptom 5 1 1 0 Insomnia 1 1 0 Depression/depressed mood 1 0 0 Adverse reactions occurring in ≥1% of subjects in the ARAKODA group in the active-control Trial 3 conducted in military personnel deployed to malaria endemic areas are presented in Table 4 .
Table 4: Selected Adverse Reactions Occurring in ≥1% of Subjects Receiving ARAKODA in Trial 3 (Deployed Subjects) Adverse Reaction ARAKODA 1 (n=492) % Mefloquine 2 (n=162) % 1 ARAKODA was administered as 200 mg daily for 3 days, then 200 mg weekly 2 Mefloquine was administered as 250 mg daily for 3 days, then 250 mg weekly 3 Includes headache, sinus headache, migraine and tension headache.
4 Includes dizziness and dizziness postural 5 Includes motion sickness, vertigo and vertigo positional.
6 Includes abnormal dreams, insomnia, nightmares, sleep disorder, and somnambulism.
7 Includes abnormal dreams, nightmares 8 Includes anxiety disorder, panic attack and stress.
Nervous system Disorders 22 27 Headache 3 15 19 Dizziness 4 1 1 Ear and labyrinth Disorders 7 11 Motion sicknesss 5 5 6 Musculoskeletal and connective tissue disorders 29 30 Back pain 14 15 Gastrointestinal disorders 36 41 Diarrhea 18 20 Nausea 7 9 Vomiting 5 6 Psychiatric disorders 5 4 Any sleep symptom 6 4 4 Insomnia 2 1 Abnormal dreams 7 2 2 Anxiety 8 1 0 Clinically Significant Adverse Reactions in Trials 1 to 5 (Overall Safety Population) Clinically significant adverse reactions with ARAKODA (200 mg daily for 3 days, followed by 200 mg weekly) in Trials 1 to 5 (n= 825) are described below: Ocular Adverse Reactions Vortex keratopathy was reported in 21% to 93% of subjects receiving ARAKODA in the trials which included ophthalmic evaluations (Trials 3, 5, and Trial 6 (NCT # 01290601, an active-control trial in patients from Thailand with P.
vivax malaria.
The keratopathy did not result in any apparent functional visual changes and resolved within one year after drug cessation in all patients.
Retinal abnormalities were noted in less than 1% of subjects receiving ARAKODA.
A total of 7 serious ocular adverse reactions (SARs) were reported in ARAKODA-treated subjects in the trials which included ophthalmic evaluations: 5 reports of keratopathy and two reports of retinal disorders.
Laboratory Abnormalities Methemoglobinemia: Asymptomatic methemoglobin elevations were observed in 13% of subjects receiving ARAKODA.
Hemoglobin decrease: Hemoglobin decreases of ≥ 3 g/dL were observed in 2.3% of subjects receiving ARAKODA.
Adverse Reactions Reported in < 1% of Subjects Receiving ARAKODA in Trials 1 to 5 The following selected adverse reactions were reported in subjects receiving ARAKODA in Trials 1 to 5 at a rate of less than 1%.
Blood and lymphatic system disorders: hemolytic anemia, anemia, thrombocytopenia Ear and labyrinth disorders: hyperacusis, Meniere’s disease Eye disorders: night blindness, photophobia, blurred vision, visual acuity reduced, visual impairment, vitreous floaters Hepatobiliary disorders: hyperbilirubinemia, jaundice cholestatic Immune system disorders: hypersensitivity Investigations: blood bilirubin increased, blood creatinine increased, glomerular filtration rate decreased Nervous system disorders: amnesia, coordination abnormal, hyperesthesia, hypoesthesia, somnolence, syncope, tremor, visual field defect Psychiatric disorders: agitation, neurosis Skin and subcutaneous tissue disorders: urticaria.