moxidectin 10 MG/ML Injectable Solution

INDICATIONS AND USAGE Moxidectin Tablets are indicated for the treatment of onchocerciasis due to Onchocerca volvulus in adult and pediatric patients aged 4 years and older and weighing at least 13 kg [see Clinical Studies ( 14 )] . Limitations of Use: Moxidectin Tablets does not kill adult Onchocerca volvulus (O. volvulus) parasites . Follow-up evaluation is advised. The safety and efficacy of repeat administration of Moxidectin Tablets in patients with O . volvulus has not been studied. Moxidectin is an anthelmintic indicated for the treatment of onchocerciasis due to Onchocerca volvulus in adults and pediatric patients aged 4 years and older and weighing at least 13 kg. ( 1 ) Limitations of Use: Moxidectin Tablets do not kill adult Onchocerca volvulus (O. volvulus) parasites. Follow-up is advised. ( 1 ) The safety and efficacy of repeat administration of Moxidectin Tablets in patients with O . volvulus has not been studied. ( 1 )

DOSAGE AND ADMINISTRATION Recommended Dosage in Adult Patients : Take 8 mg (four 2 mg tablets) as a single oral dose, with or without food. ( 2.1 ) Recommended Dosage in Pediatric P atients (4 Years of Age and Older and Weighing at Least 13 kg): See Table below. ( 2.2 ) Body Weight Dose Number of 2 mg Tablets 13 kg to less than 15 kg 4 mg 2 15 kg to less than 30 kg 6 mg 3 Greater than or equal to 30 kg 8 mg 4 2.1 Recommended Dosage in Adult Patients The recommended dosage of Moxidectin Tablets in adult patients is a single dose of 8 mg (four 2 mg tablets) taken orally with or without food [see Clinical Pharmacology ( 12.3 )]. 2. 2 Recommended Dosage in Pediatric Patients (4 Years of Age and Older and Weighing at Least 13 kg) The recommended dosage of Moxidectin Tablets in pediatric patients aged 4 years and older and weighing at least 13 kg is described in Table 1 below. Administer Moxidectin Tablets as a single dose taken orally with or without food [see Clinical Pharmacology ( 12.3 ) ]. Table 1: Recommended Dosage of Moxidectin Tablets in Pediatric Patients 4 Years of Age and Older and Weighing at Least 13 kg Body Weight Dose Number of 2 mg Tablets 13 kg to less than 15 kg 4 mg 2 15 kg to less than 30 kg 6 mg 3 Greater than or equal to 30 kg 8 mg 4

WARNINGS AND PRECAUTIONS Cutaneous, Ophthalmological and/or Systemic Adverse Reactions of Varying Severity (Mazzotti Reaction ) : This may occur in patients with onchocerciasis following treatment with Moxidectin Tablets. Monitor patients for symptoms, including symptomatic orthostatic hypotension. ( 5.1 ) Symptomatic Orthostatic Hypotension : Episodes of symptomatic orthostatic hypotension including inability to stand without support may occur in patients following treatment with Moxidectin Tablets. ( 5.2 ) Encephalopathy in Loa loa C o- I nfected P atients : Serious or even fatal encephalopathy following treatment with Moxidectin Tablets may occur in patients co-infected with Loa loa . Assess patients for loiasis in Loa loa endemic areas prior to treatment. ( 5.3 ) Edema and Worsening of Onchodermatitis : Patients with hyper-reactive onchodermatitis (sowda) may be more likely than others to experience severe edema and aggravation of onchodermatitis. ( 5.4 ) 5.1 Cutaneous, Ophthalmological and/or Systemic Adverse Reactions Treatment with Moxidectin Tablets may cause cutaneous, ophthalmological and/or systemic reactions of varying severity (Mazzotti reaction). These adverse reactions are due to allergic and inflammatory host responses to the death of microfilariae [see Adverse Reactions ( 6.1 )]. There is a trend toward an increased incidence of these adverse reactions in patients with higher microfilarial burden. The clinical manifestations of Mazzotti reaction include pruritus, headache, pyrexia, rash, urticaria, hypotension (including symptomatic orthostatic hypotension and dizziness) [ see Warnings and Precautions ( 5.2 )] , tachycardia, edema, lymphadenopathy, arthralgia, myalgia, chills, paresthesia and asthenia. Ophthalmological manifestations include conjunctivitis, eye pain, eye pruritus, eyelid swelling, blurred vision, photophobia, changes in visual acuity, hyperemia, ocular discomfort and watery eyes. These adverse reactions generally occur and resolve in the first week post-treatment. Laboratory changes include eosinophilia, eosinopenia, lymphocytopenia, neutropenia, and increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH). Proteinuria has also been reported. Treatment of severe Mazzotti reactions has not been evaluated in controlled clinical trials. Symptomatic treatments such as oral hydration, recumbency, intravenous normal saline, and/or parenteral corticosteroids have been used to treat orthostatic hypotension. Antihistamines and/or analgesics have been used for most mild to moderate cases. 5.2 Symptomatic Orthostatic Hypotension An increased number of patients who received Moxidectin Tablets developed symptomatic orthostatic hypotension with inability to stand without support after lying down for 5 minutes (in an orthostatic hypotension provocation test); 47/978 (5%) compared with 8/494 (2%) who received ivermectin. The decreases in blood pressure were transient, managed by resumption of recumbency and most commonly occurred on Days 1 and 2 post-treatment. Advise patients that if they feel dizzy or light-headed after taking Moxidectin Tablets, they should lie down until the symptoms resolve. 5.3 Encephalopathy in Loa loa Co - infected Patients Patients with onchocerciasis who are also infected with Loa loa may develop a serious or even fatal encephalopathy following treatment with Moxidectin Tablets. Moxidectin Tablets have not been studied in patients co-infected with Loa loa . Therefore, it is recommended that individuals who warrant treatment with Moxidectin Tablets and have had exposure to Loa loa -endemic areas undergo diagnostic screening for loiasis prior to treatment. 5.4 Edema and Worsening of Onchodermatitis Patients with hyper-reactive onchodermatitis (sowda) may be more likely than others to experience severe edema and worsening of onchodermatitis following the use of Moxidectin Tablets. Symptomatic treatment has been used to manage patients who have experienced edema and worsening of onchodermatitis.

CONTRAINDICATIONS None. None. ( 4 )

Mechanism of Action Moxidectin, a macrocyclic lactone, is an anthelmintic drug [see Microbiology ( 12.4 )] .