TPOXX

TPOXX- tecovirimat monohydrate capsule
SIGA Technologies, Inc.

1 INDICATIONS AND USAGE

1.1 Treatment of Human Smallpox Disease

TPOXX® is indicated for the treatment of human smallpox disease caused by variola virus in adults and pediatric patients weighing at least 13 kg.

1.2 Limitations of Use

The effectiveness of TPOXX for treatment of smallpox disease has not been determined in humans because adequate and well-controlled field trials have not been feasible, and inducing smallpox disease in humans to study the drug’s efficacy is not ethical [see Clinical Studies (14)].

TPOXX efficacy may be reduced in immunocompromised patients based on studies demonstrating reduced efficacy in immunocompromised animal models.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage for Adults and Pediatric Patients Weighing at Least 40 kg

The recommended dosage of TPOXX in adults and pediatric patients weighing at least 40 kg is 600 mg (three 200 mg capsules) taken twice daily orally for 14 days. TPOXX should be taken within 30 minutes after a full meal of moderate or high fat [see Clinical Pharmacology (12.3)].

2.2 Dosage for Pediatric Patients

The recommended dosage for pediatric patients is based on weight starting at 13 kg as shown in Table 1. The dose should be given twice daily orally for 14 days and should be taken within 30 minutes after a full meal of moderate or high fat [see Clinical Pharmacology (12.3)].

2.3 Preparation for Administration to Pediatrics and Those Who Cannot Swallow Capsules

TPOXX capsules can be administered by carefully opening the capsule and mixing the entire contents in 30 mL of liquid (e.g., milk, chocolate milk) or soft food (e.g., apple sauce, yogurt). The entire mixture should be administered within 30 minutes of its preparation.

Table 1: Recommended Pediatric and Adult Dosage and Preparation Instructions
Body Weight Dosage Number of Capsules Drug-Food Preparation
13 kg to less than 25 kg 200 mg twice daily Contents of 1 Capsule twice daily Mix 1 capsule of TPOXX with 30 mL of liquid or soft food. Administer the whole mixture.
25 kg to less than 40 kg 400 mg twice daily Contents of 2 Capsules twice daily Mix 2 capsules of TPOXX with 30 mL of liquid or soft food. Administer the whole mixture.
40 kg and above 600 mg twice daily Contents of 3 Capsules twice daily Mix 3 capsules of TPOXX with 30 mL of liquid or soft food. Administer the whole mixture.

3 DOSAGE FORMS AND STRENGTHS

TPOXX capsules are hard gelatin with an opaque orange body imprinted in white ink with “SIGA” followed by the SIGA logo followed by “®”, and an opaque black cap imprinted in white ink with “ST-246® ”, containing white to off-white powder. Each capsule contains 200 mg of tecovirimat.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Hypoglycemia When Co-Administered with Repaglinide

Co-administration of repaglinide and tecovirimat may cause mild to moderate hypoglycemia. Monitor blood glucose and monitor for hypoglycemic symptoms when administering TPOXX with repaglinide [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

In a drug interaction study, 10 of 30 healthy subjects experienced mild (6 subjects) or moderate (4 subjects) hypoglycemia following co-administration of repaglinide (2 mg) and TPOXX. Symptoms resolved in all subjects after intake of food and/or oral glucose.

6 ADVERSE REACTIONS

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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of TPOXX has not been studied in patients with smallpox disease.

The safety of TPOXX was evaluated in 359 healthy adult subjects ages 18-79 years in a Phase 3 clinical trial. Of the subjects who received at least one 600 mg dose of TPOXX, 59% were female, 69% were White, 28% were Black/African American, 1% were Asian, and 12% were Hispanic or Latino. Ten percent of the subjects who participated in the study were age 65 or older. Of these 359 subjects, 336 subjects received at least 23 of 28 doses of 600 mg TPOXX in a twice daily regimen for 14 days.

Most Frequently Reported Adverse Reactions

The most frequently reported adverse reactions were headache and nausea. Adverse reactions that occurred in at least 2% of subjects in the TPOXX treatment group are shown in Table 2.

Table 2: Adverse Reactions Reported in ≥ 2% of Healthy Adult Subjects Receiving at Least One Dose of TPOXX 600 mg

a Includes abdominal pain, abdominal pain upper, abdominal distension, abdominal discomfort, abdominal painlower, epigastric pain

Adverse Reaction TPOXX 600 mgN = 359(%) PlaceboN = 90(%)
Headache 12 8
Nausea 5 4
Abdominal paina 2 1
Vomiting 2 0

Adverse Reactions Leading to Discontinuation of TPOXX

Six subjects (2%) had their treatment with TPOXX discontinued due to adverse reactions. Each of these subject’s adverse reactions (with severity) is listed below:

  • EEG change, abnormal
  • Mild upset stomach, dry mouth, decreased concentration and dysphoria
  • Mild nausea and fever, moderate diarrhea, severe headache
  • Mild palpable purpura
  • Mild nausea, fever and chills
  • Mild facial redness, facial swelling and pruritus

Less Common Adverse Reactions

Clinically significant adverse reactions that were reported in < 2% of subjects exposed to TPOXX and at rates higher than subjects who received placebo are listed below:

  • Gastrointestinal: dry mouth, chapped lips, dyspepsia, eructation, oral paresthesia
  • General and administration site: pyrexia, pain, chills, malaise, thirst
  • Investigations: abnormal electroencephalogram, hematocrit decreased, hemoglobin decreased, heart rate increased
  • Musculoskeletal and connective tissue: arthralgia, osteoarthritis
  • Nervous system: migraine, disturbance in attention, dysgeusia, paresthesia
  • Psychiatric: depression, dysphoria, irritability, panic attack
  • Respiratory, Thoracic and Mediastinal Disorders: oropharyngeal pain
  • Skin and subcutaneous tissue: palpable purpura, rash, pruritic rash, facial redness, facial swelling, pruritus

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