o 120 kg and above: 300 mg every 12 hours by intravenous infusion over
6 hours for up to 14 days.
 Pediatric patients weighing 13 kg or more should be switched to TPOXX
Capsules to complete the 14-day treatment course as soon as oral therapy
can be tolerated.
 Administration Instruction for TPOXX Capsules: Take within 30 minutes
after a full meal containing moderate or high fat. (2.1, 2.3)
 Administration Instructions for TPOXX Injection: Infuse over 6 hours via
infusion pump. (2.5)
 See Full Prescribing Information for additional information on theadministration and preparation of TPOXX Capsules and Injection. (2)HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
TPOXX® safely and effectively. See full prescribing information for
TPOXX.
TPOXX (tecovirimat) capsules, for oral use
TPOXX (tecovirimat) injection, for intravenous use
Initial U.S. Approval: 2018
RECENT MAJOR CHANGES
Indications and Usage (1.1)
Dosage and Administration (2.1, 2.2, 2.3, 2.4, 2.5)
Contraindications (4)Warnings and Precautions (5.2)

5/2022
5/2022
5/2022
5/2022DOSAGE FORMS AND STRENGTHS
Capsules 200 mg of tecovirimat (2.4)
Injection
 A single-dose vial containing 200 mg of tecovirimat in 20 mL for further
dilution prior to intravenous infusion. (3)

INDICATIONS AND USAGETPOXX is an inhibitor of the orthopoxvirus VP37 envelope wrapping protein
and is indicated for the treatment of human smallpox disease in adults andpediatric patients weighing at least 3 kg. (1.1)
Limitations of Use: The effectiveness of TPOXX for treatment of smallpox disease has notbeen determined in humans because adequate and well controlled fieldtrials have not been feasible, and inducing smallpox disease in humans tostudy the drug’s efficacy is not ethical. (1.2)
 TPOXX efficacy may be reduced in immunocompromised patients basedon studies demonstrating reduced efficacy in immunocompromised animalmodels. (1.2)

CONTRAINDICATIONS TPOXX capsules: None TPOXX injection: TPOXX Injection is contraindicated in patients withsevere renal impairment (defined as creatinine clearance below 30 mL/min)(4, 5.2)

DOSAGE AND ADMINISTRATION
 Pediatric and Adult Patients weighing 40 kg or more (2.3) (Oral Dosing):o 40 kg to less than 120 kg: 600 mg of TPOXX every 12 hours for
14 dayso 120 kg or more: 600 mg of TPOXX every 8 hours for 14 days
 Pediatrics and adult patients weighing 13 kg or more and those who cannot
swallow capsules (2.3) (Oral Dosing): TPOXX Capsules can beadministered by carefully opening the number of capsule noted below andmixing and administering the entire contents in 30 mL of liquid (e.g., milk,
chocolate milk) or soft food (e.g., apple sauce, yogurt):
o 13 kg to less than 25 kg: 200 mg (1 Capsule) of TPOXX every 12 hours
for 14 dayso 25 kg to less than 40 kg: 400 mg (2 Capsules) of TPOXX every
12 hours for 14 dayso 40 kg to less than 120 kg: 600 mg (3 Capsules) of TPOXX every
12 hours for 14 days.
o 120 kg or more: 600 mg (3 capsules) every 8 hours for 14 days
 Patients weighing 3 kg and above (2.5) (Intravenous Dosing):o 3 kg to less than 35 kg: 6 mg/kg every 12 hours by intravenous infusion
over 6 hours for up to 14 dayso 35 kg to less than 120 kg: 200 mg every 12 hours by intravenous
infusion over 6 hours for up to 14 days
FULL PRESCRIBING INFORMATION: CONTENTS*
INDICATIONS AND USAGE
1.
1.1. Treatment of Human Smallpox Disease
1.2. Limitations of Use
2.
DOSAGE AND ADMINISTRATION
2.1. Important Dosing Instructions
2.2. Testing Before Initiating and During Treatment with TPOXXInjection
2.3. TPOXX Oral Dosage for Pediatric Patients Weighing at Least 13
kg and Adults
2.4. Renal Impairment
2.5. Dosage and Administration of TPOXX Injection for Intravenous
Infusion
3.
DOSAGE FORMS AND STRENGTHS
4.
CONTRAINDICATIONS5.
WARNINGS AND PRECAUTIONS
5.1. Hypoglycemia When Co-Administered with Repaglinide
5.2. Risks of Hydroxypropyl-β-Cyclodextrin Excipient for Patientswith Renal Insufficiency and Pediatric Patients < 2 Years of age
6.
ADVERSE REACTIONS
6.1. Clinical Trials Experience
7.
DRUG INTERACTIONS
7.1. Effect of TPOXX on Other Drugs
7.2. Established Drug Interactions
7.3. Drugs Without Clinically Significant Interactions With TPOXX

1Reference ID: 4985981

WARNINGS AND PRECAUTIONS
Hypoglycemia: Co administration with repaglinide may cause hypoglycemia.
Monitor blood glucose and monitor for hypoglycemic symptoms duringco-administration. (5.1)
ADVERSE REACTIONS
The most common adverse reactions are:
 TPOXX Capsules (incidence ≥ 2%): headache, nausea, abdominal pain,
and vomiting. (6.1)
 TPOXX Injection (incidence ≥ 4%): administration site reactions andheadache. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact SIGA
Technologies Inc. at 1-888-899-3472 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
DRUG INTERACTIONS
Consult the full prescribing information prior to and during treatment forpotential drug interactions. (5.1, 7, 12.3)
USE IN SPECIFIC POPULATIONS
Lactation: Breastfeeding is not recommended in patients with smallpox. (8.2)
See 17 for PATIENT COUNSELING INFORMATION
Revised: 05/2022

8.

10.
11.
12.

13.
14.
16.
17.

7.4. Vaccine Interactions
USE IN SPECIFIC POPULATIONS
8.1. Pregnancy
8.2. Lactation
8.3. Females and Males of Reproductive Potential
8.4. Pediatric Use
8.5. Geriatric Use
8.6. Renal Impairment
8.7. Hepatic Impairment
OVERDOSAGEDESCRIPTION
CLINICAL PHARMACOLOGY
12.1. Mechanism of Action
12.2. Pharmacodynamics
12.3. Pharmacokinetics
12.4. Microbiology
NONCLINICAL TOXICOLOGY
13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2. Animal Toxicology and/or Pharmacology
CLINICAL STUDIESHOW SUPPLIED/STORAGE AND HANDLINGPATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing information
are not listed.

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FULL PRESCRIBING INFORMATION
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 inadults and pediatric patients weighing at least 3 kg.

1.2.

Limitations of Use

The effectiveness of TPOXX for treatment of smallpox disease has not been determined inhumans 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.

Important Dosing Instructions

It is recommended that patients 13 kg and above initiate oral treatment with TPOXX capsules if
possible. If patients are unable to take oral TPOXX capsules or Drug-Food Preparation,
treatment may be initiated with TPOXX injection as a 6 hour intravenous (IV) infusion. If IV
treatment is necessary, conversion from IV to oral TPOXX is recommended as soon as oral
treatment can be tolerated [see Dosage and Administration (2.3)]. In patients receiving an IV
infusion, the first dose of oral treatment should be given at the time of and in place of the nextscheduled IV dosing.
In patients receiving an oral treatment who subsequently require IV treatment, the first dose of
IV infusion should be given at the time of and in place of the next scheduled oral dosing.
TPOXX capsules
Take TPOXX capsules within 30 minutes after a full meal containing moderate or high fat.
Missed DoseIf a dose of oral TPOXX is missed, the patient should take the dose as soon as possible andanytime up to 8 hours prior to the next scheduled dose. If less than 8 hours remain before thenext scheduled dose, do not take the missed dose, and resume dosing at the next scheduled dose.
TPOXX injection
Administer TPOXX injection by IV infusion over 6 hours via an infusion pump. Must dilute
TPOXX Injection prior to use [see Dosage and Administration (2.5)].

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2.2.

Testing Before Initiating and During Treatment with TPOXXInjection

Determine creatinine clearance in all patients before starting TPOXX injection and monitor
while receiving TPOXX injection as clinically appropriate [see Dosage and Administration (2.4),
Contraindications (4), Warnings and Precautions (5.2) and Use in Specific Populations (8.4,8.6)].

2.3.

TPOXX Oral Dosage for Pediatric Patients Weighing at Least 13 kg
and Adults

The recommended dosage of TPOXX capsules in pediatric patients weighing at least 13 kg andadults is displayed in Table 1 below.
Table 1:

Recommended Dosage and Preparation Instructions for TPOXX Capsules in
Pediatric Patients Weighing at Least 13 kg and Adults

Body Weight

Oral Dosage for 14 Daysa
Dosage (Number of Capsules)

13 kg to less than 25 kga

200 mg (1 capsule) every
12 hours

25 kg to less than 40 kg

400 mg (2 capsules) every
12 hours

40 kg to less than 120 kg

600 mg (3 capsules) every
12 hours

120 kg and above

600 mg (3 capsules) every
8 hours

Drug Food Preparation for Patients
Who Cannot Swallow Capsules
Carefully open the required number ofcapsules and mix contents of capsule(s)of TPOXX with 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.

TPOXX capsules should be taken within 30 minutes after a full meal containing moderate or high fat [see ClinicalPharmacology (12.3)]

2.4.

Renal Impairment

TPOXX injection is contraindicated in patients with creatinine clearance below 30 mL per
minute [see Contraindications (4)].

2.5.

Dosage and Administration of TPOXX Injection for Intravenous
Infusion

The recommended dosage of TPOXX injection in pediatric patients weighing at least 3 kg andadults is displayed in Table 2 below.
TPOXX injection is supplied in a single-dose clear glass vial containing 200 mg/20 mL(10 mg/mL). Parenteral drug products must be inspected visually for particulate matter anddiscoloration prior to administration, whenever solution and container permit. To administer:

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

Use aseptic technique when preparing TPOXX injection.

Withdraw the quantity of TPOXX injection (Table 2), add this volume to the syringe thendilute with two equal parts of either 0.9% (w/v) sodium chloride injection (normal saline)
or 5% (w/v) dextrose injection in a syringe of suitable size. Injection with diluents otherthan 0.9% sodium chloride or 5% dextrose solution has not been studied. NOT FOR IV
BOLUS INJECTION. Do not use prefilled infusion bags for product preparation
and administration.



The diluted TPOXX injection may be stored refrigerated (2°C - 8°C) for up to 24 hours
or at room temperature (15°C - 25°C) for up to 4 hours.



Gently swirl the syringe of in-use solution prior to inserting into the syringe pump andinfuse over 6 hours every 12 hours for 14 days.



Do not re-use the single-dose vial once it has been punctured.

Table 2:

Recommended Pediatric and Adult Dosage and Preparation Instructions
TPOXX Injection for IV Infusiona

Body Weight

Dosage for up to 14 days

Volume of
TPOXX Injectionb

Volume ofDiluentc

3 kg to less than 35 kg

6 mg/kg every 12 hours byintravenous infusion over 6 hoursa

0.6 mL/kg

1.2 mL/kg

35 kg to less than 120 kg

200 mg every 12 hours byintravenous infusion over 6 hours

20 mL

40 mL

120 kg and aboved

300 mg every 12 hours byintravenous infusion over 6 hours

30 mL

60 mL

a

Patients weighing at least 13 kg should be switched to TPOXX Capsules to complete the 14 day treatment course assoon as oral therapy can be tolerated.
b
10 mg/mL TPOXX solution containing 40% hydroxypropyl betadex (8 g per vial) with water for injection[see Dosage Forms and Strengths (3)].
cDiluent is either 0.9% (w/v) sodium chloride injection or 5% (w/v) dextrose injection solution.
d
Depending on size of syringe available with syringe pump system, two separate syringes may be needed for each
6 hour administration.

3.

DOSAGE FORMS AND STRENGTHSTPOXX Capsules
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 inwhite ink with “ST-246®”, containing white to off-white powder. Each capsule contains 200 mg
of tecovirimat.

TPOXX Injection
TPOXX injection: 200 mg/20 mL (10 mg/mL) of tecovirimat as a clear, colorless to pale yellow
solution in a single-dose vial for further dilution.

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4.

CONTRAINDICATIONSTPOXX Capsules:
None.
TPOXX Injection:
The excipient hydroxypropyl-β-cyclodextrin is eliminated through glomerular filtration.
Therefore, TPOXX Injection is contraindicated in patients with severe renal impairment (definedas creatinine clearance below 30 mL/min). [see Warnings and Precautions (5.2) and Use inSpecific Populations (8.6)]

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 (7.2) 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
capsules. Symptoms resolved in all subjects after intake of food and/or oral glucose.

5.2.

Risks of Hydroxypropyl-β-Cyclodextrin Excipient for Patients with
Renal Insufficiency and Pediatric Patients < 2 Years of age

Patients with renal insufficiency
TPOXX Injection: In healthy patients and in patients with mild to severe renal insufficiency, themajority of an 8 g dose of hydroxypropyl-β-cyclodextrin (per 200 mg tecovirimat/20 mL
solution) is eliminated in the urine. It is known that clearance of hydroxypropyl-β-cyclodextrin
is reduced in patients with mild, moderate, and severe renal impairment, resulting in higher
exposure to hydroxypropyl-β-cyclodextrin; in these patients, half-life values are increased overnormal values by approximately two-, four-, and six-fold, respectively. In these patients,
successive infusions may result in accumulation of hydroxypropyl-β-cyclodextrin until steadystate is reached.
In patients with mild (defined as creatinine clearance 60-89 mL/min) and moderate (defined as
creatinine clearance 30-59 mL/min) renal impairment, TPOXX Injection should be used withcaution. Creatinine clearance should be closely monitored and, if renal toxicity is suspected,
consideration should be given to administering TPOXX orally if possible or to using analternative medication. TPOXX Injection is contraindicated in patients with severe renal
impairment (creatinine clearance <30 mL/min) [see Contraindications (4) and ClinicalPharmacology (12.3)].

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Pediatric patientsTPOXX Injection: In pediatric patients less than 2 years of age, there are limited data regarding
the use of hydroxypropyl-β-cyclodextrin. Given that renal tubular function rapidly matures overthe first few years of life, clearance of hydroxypropyl-β-cyclodextrin may be reduced in young
pediatric patients, resulting in higher exposure to hydroxypropyl-β-cyclodextrin. TPOXXInjection should be used with caution in this population given that animal studies have shown
potential for nephrotoxicity at very high exposure levels of hydroxypropyl-β-cyclodextrin.
Given the potential for drug accumulation due to renal immaturity in pediatric patients less than
2 years, monitoring of renal function after treatment is recommended [see Use in Specific
Populations (8.4) and Clinical Pharmacology (12.3)].

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 trialsof another drug and may not reflect the rates observed in practice.
The safety of TPOXX has not been studied in patients with smallpox disease.
TPOXX Clinical Trial (Oral Administration)
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% werefemale, 69% were White, 28% were Black/African American, 1% were Asian, and 12% wereHispanic or Latino. Ten percent of the subjects who participated in the study were age 65 orolder. Of these 359 subjects, 336 subjects received at least 23 of 28 doses of 600 mg TPOXX ina twice daily (every 12 hours) 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 3.
Table 3:aTreatment-Related Adverse Reactions Reported in ≥ 2% of Healthy Adult
Subjects Receiving at Least One Dose of TPOXX Capsules 600 mg

Adverse Reaction

TPOXX 600 mg
N = 359(%)

Placebo
N = 90(%)

Headache12

8

Nausea5

4

Abdominal paina

2

1

Vomiting

20Includes abdominal pain, abdominal pain upper, abdominal distension, abdominal discomfort, abdominal pain
lower, epigastric pain

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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, facialswelling, pruritus

TPOXX Clinical Trial (Intravenous Administration)
The safety of multiple doses of 240 mg of TPOXX injection for IV infusion was evaluated in
26 healthy adult subjects ages 23-62 years, inclusive. An additional 6 subjects received placebo.
TPOXX injection was administered over a 6 hour period via infusion pump twice daily (every
12 hours) for 7 days. Of the 26 subjects administered TPOXX, 42% were female, 69% wereWhite, 23% were Black/African American, and 42% were Hispanic or Latino.
Most Frequently Reported Adverse Reactions
The most frequently reported adverse reactions included infusion site pain, infusion site swelling,
infusion site erythema, infusion site extravasation, and headache. Adverse reactions that
occurred in at least 4% of subjects in the TPOXX treatment group are shown in Table 4.

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Table 4:

Treatment-Related Adverse Reactions Reported in ≥ 4% of Healthy Adult
Subjects Receiving at Least One Dose of TPOXX Injection 240 mg
TPOXX 240 mg
N =26
(%)

Infusion Site Pain
Infusion Site Swelling
Infusion Site Erythema
Infusion Site Extravasation
Headache

73
39
23
19
15

Placebo
N=6
(%)
67
67
67
50
0

Adverse Reactions Leading to Discontinuation of TPOXX Injection
Three subjects (12%) had their treatment with TPOXX injection discontinued due to adverse
reactions. One subject had two adverse reactions. Each of these subject’s adverse reactions(with severity) are listed below:Moderate Infusion site extravasation



Mild Infusion site extravasation



Mild Infusion site swelling and mild infusion site pain

Less Common Adverse Reactions
Clinically significant adverse reactions that were reported in < 4% of subjects exposed to
TPOXX injection and at rates higher than subjects who received placebo are listed below:


General and administration site: infusion site discomfort, infusion site edemaMusculoskeletal and connective tissue: myalgia, arthritis, back pain, muscle tightness

Gastrointestinal: diarrhea



Eye: photophobia

Skin and Subcutaneous Tissue: pruritus generalized

7.

DRUG INTERACTIONS

7.1.

Effect of TPOXX on Other Drugs

Tecovirimat is a weak inducer of cytochrome P450 (CYP)3A and a weak inhibitor of CYP2C8
and CYP2C19. However, the effects are not expected to be clinically relevant for mostsubstrates of those enzymes based on the magnitude of interactions and the duration of treatmentof TPOXX. See Table 5 for clinical recommendations for select sensitive substrates.

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7.2.

Established Drug Interactions

Table 5 provides a listing of established or significant drug interactions [see Warnings andPrecautions (5.1) and Clinical Pharmacology (12.3)].
Table 5:Significant Drug Interactions

Concomitant Drug
Effect on
Class: Drug Name
Concentrationa
Blood Glucose-Lowering Agent:
Repaglinideb
repaglinide

CNS Depressant:Midazolambamidazolam

Clinical Effect/Recommendation

Monitor blood glucose and monitor for
hypoglycemic symptoms in patients when TPOXX
is co-administered with repaglinide[see Warnings and Precautions (5.1)].
Monitor for effectiveness of midazolam.

↓ = decrease, ↑ = increase
These interactions have been studied in healthy adults.

b

7.3.

Drugs Without Clinically Significant Interactions With TPOXXBased on a drug interaction study, no clinically significant drug interactions have been observed
when TPOXX is co-administered with bupropion, flurbiprofen, or omeprazole [see ClinicalPharmacology (12.3)].

7.4.

Vaccine Interactions

No vaccine-drug interaction studies have been performed in human subjects. Some animalstudies have indicated that co-administration of TPOXX at the same time as live smallpox
vaccine (vaccinia virus) may reduce the immune response to the vaccine. The clinical impact of
this interaction on vaccine efficacy is unknown.

8.

USE IN SPECIFIC POPULATIONS

8.1.

Pregnancy

Risk Summary
There are no available data on the use of tecovirimat in pregnant individuals to evaluate for adrug-associated risk of major birth defects, miscarriage, and other adverse maternal and fetal
outcomes.
In animal reproduction studies, no embryofetal developmental toxicity was observed in mice
during the period of organogenesis at tecovirimat exposures (area under the curve [AUC]) up to
23 times higher than human exposure at the recommended human dose (RHD). In rabbits, noembryofetal developmental toxicity was observed during organogenesis at tecovirimat exposures(AUC) less than human exposures at the RHD. In a mouse pre-/post-natal development study,
no toxicities were observed at maternal tecovirimat exposures up to 24 times higher than human
exposure at the RHD (see Data).
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The background risk of major birth defects and miscarriage for the indicated population is
unknown, and the estimated background risk of miscarriage for the indicated population is higher
than the general population. All pregnancies have a background risk of birth defect, loss or otheradverse outcomes. In the U.S. general population, the estimated background risk of major birthdefects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
Tecovirimat was administered orally to pregnant mice at doses up to 1,000 mg/kg/day fromgestation Days 6-15. No embryofetal toxicities were observed at doses up to 1,000 mg/kg/day(approximately 23 times higher than human exposure at the RHD).
Tecovirimat was administered orally to pregnant rabbits at doses up to 100 mg/kg/day fromgestation Days 6-19. No embryofetal toxicities were observed at doses up to 100 mg/kg/day(0.4 times the human exposure at the RHD).
In the pre-/post-natal development study, tecovirimat was administered orally to pregnant miceat doses up to 1,000 mg/kg/day from gestation Day 6 to post-natal Day 20. No toxicities wereobserved at doses up to 1,000 mg/kg/day (approximately 24 times higher than human exposure at
the RHD).

8.2.

Lactation

Risk Summary
Because of the potential for variola virus transmission through direct contact with the breastfed
infant, breastfeeding is not recommended in patients with smallpox. There are no data on thepresence of tecovirimat in human milk, the effects of the drug on the breastfed infant, or on milk
production. Tecovirimat was present in animal milk (see Data). When a drug is present inanimal milk, it is likely to be present in human milk.
Data
In a lactation study at doses up to 1,000 mg/kg/day, mean tecovirimat milk to plasma ratios up to
approximately 0.8 were observed at 6 and 24 hours post-dose when administered orally to miceon lactation Day 10 or 11.

8.3.

Females and Males of Reproductive Potential

Infertility
There are no data on the effect of tecovirimat on human fertility. Decreased fertility due totesticular toxicity was observed in male mice [see Nonclinical Toxicology (13.1)].

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8.4.

Pediatric Use

As in adults, the effectiveness of TPOXX in pediatric patients is based solely on efficacy studies
in animal models of orthopoxvirus disease. As exposure of healthy pediatric subjects to TPOXX
with no potential for direct clinical benefit is not ethical, pharmacokinetic simulation was used toderive dosing regimens that are predicted to provide pediatric patients with exposurescomparable to the observed exposure in adults receiving 600 mg orally twice daily (every
12 hours) or 200 mg intravenously twice daily (every 12 hours). The dosage for pediatricpatients is based on weight [see Dosage and Administration (2.2) and Clinical Pharmacology(12.3)].
TPOXX Injection:
There are limited data regarding the use of hydroxypropyl-β-cyclodextrin, an ingredient in
TPOXX injection, in pediatric patients less than 2 years of age. Given the potential for drug
accumulation due to renal immaturity in pediatric patients less than 2 years, monitoring of renal
function after treatment is recommended [see Warnings and Precautions (5.2) and ClinicalPharmacology (12.3)].

8.5.

Geriatric Use

Clinical studies of TPOXX did not include sufficient numbers of subjects aged 65 and over todetermine whether the safety profile of TPOXX is different in this population compared toyounger subjects. Of the 359 subjects in the clinical study of oral TPOXX, 10% (36/359) were
≥ 65 years of age, and 1% (4/359) were ≥ 75 years of age. No alteration of dosing is needed forpatients ≥ 65 years of age [see Clinical Pharmacology (12.3)].

8.6.

Renal Impairment

TPOXX Capsules:
No dosage adjustment is required for patients with mild, moderate or severe renal impairment or
patients with end stage renal disease (ESRD) requiring hemodialysis [see Clinical Pharmacology(12.3)].
TPOXX Injection:
Hydroxypropyl-β-cyclodextrin, an ingredient in TPOXX injection, when administeredintravenously, is eliminated through glomerular filtration. No dosage adjustment is required forpatients with mild (creatinine clearance 60-89 mL/min) or moderate (creatinine clearance
30-59 mL/min) renal impairment. TPOXX Injection is contraindicated in patients with severe
renal impairment (creatinine clearance below 30 mL/min) [see Contraindications (4)].

8.7.

Hepatic Impairment

No dosage adjustment is required for patients with mild, moderate or severe hepatic impairment(Child Pugh Class A, B, or C) [see Clinical Pharmacology (12.3)].

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10.

OVERDOSAGE

There is no clinical experience with overdosage of TPOXX. In case of overdosage, monitor
patients for any signs or symptoms of adverse effects. Hemodialysis will not significantly
remove TPOXX in overdosed patients.

11.

DESCRIPTIONTPOXX capsules and TPOXX injection contains tecovirimat, an inhibitor of the orthopoxvirus
VP37 envelope wrapping protein.
TPOXX (tecovirimat) capsules, for oral use are immediate release capsules containing
tecovirimat monohydrate equivalent to 200 mg of tecovirimat for oral administration.
The capsules include the following inactive ingredients: colloidal silicon dioxide,
croscarmellose sodium, hydroxypropyl methyl cellulose, lactose monohydrate, magnesium
stearate, microcrystalline cellulose, and sodium lauryl sulfate. The capsule shell is composed ofgelatin, FD&C blue #1, FD&C red #3, FD&C yellow #6, and titanium dioxide.
TPOXX (tecovirimat) injection, for intravenous use is a sterile, colorless to pale yellow solution
free of visible particles that is intended for intravenous use following dilution. Tecovirimat
injection is available in a single-dose vial containing 200 mg/20 mL (10 mg/mL) of tecovirimat
and 8,000 mg (400 mg/mL) of Hydroxypropyl Betadex, NF (hydroxypropyl β-cyclodextrin) and
Water for Injection, USP/NF.
Tecovirimat monohydrate is a white to off-white crystalline solid with the chemical nameBenzamide, N-[(3aR,4R,4aR,5aS,6S,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6ethenocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl), rel-(monohydrate). The chemical
formula is C19H15F3N2O3ꞏH2O representing a molecular weight of 394.35 g/mol. The molecular
structure is as follows:

Tecovirimat monohydrate is practically insoluble in water and across the pH range of
2.0-6.5 (< 0.1 mg/mL).

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12.

CLINICAL PHARMACOLOGY

12.1.

Mechanism of Action

Tecovirimat is an antiviral drug against variola (smallpox) virus [see Microbiology (12.4)].

12.2.

Pharmacodynamics

Cardiac Electrophysiology
TPOXX does not prolong the QT interval to any clinically relevant extent at the anticipatedtherapeutic exposure.

12.3.

Pharmacokinetics

At the recommended oral dosage of 600 mg every 12 hours administered in healthy adults
weighing less than 120 kg, the mean steady-state values of tecovirimat AUC0-24hr, Cmax, andCtau/trough are 29816 hrꞏng/mL (n, CV: 43, 34%), 2159 ng/mL (n, CV: 46, 32%), and 845 ng/mL(n, CV: 45, 47%), respectively. At the recommended intravenous dosage of 200 mg every
12 hours administered by IV infusion over 6 hours in healthy adults, the mean steady-state valuesof tecovirimat AUC0-24hr, Cmax, and Cmin are 39405 hr.ng/mL (n, CV: 22, 23%), 2630 ng/mL(n, CV: 22, 22%), and 747 ng/mL (n, CV: 22, 29%). Refer to Table 6 for pharmacokinetic
parameters of tecovirimat. Tecovirimat steady-state is achieved by Day 4-6.
Table 6:

Pharmacokinetic Properties of Tecovirimat

Absorption
200 mg intravenous 600 mg oral
Median Tmax (h) (Range)
6 (6-6.5)
6 (2-24)a
Effect of food (relative to fasting)NA↑39% bDistribution% Bound to human plasma proteins
77-82
Blood-to-plasma ratio
0.62-0.90(drug or drug-related materials)
Volume of distribution (Vz or Vz/F, L) (CV%)
383 (46%)
1030
Metabolism
Metabolic pathwaysc
Hydrolysis, UGT1A1d, UGT1A4
Elimination
Major route of elimination
Metabolism
Clearance (CL or CL/F, L/hr) (CV%)
13 (23%)31
t½ (h)e (CV%)
21 (45%)19(29%)% of dose excreted in urinefNA73, predominantly as metabolitesf% of dose excreted in fecesNA23, predominantly as tecovirimata
Value reflects administration of drug with food.
b
Value refers to mean systemic exposure (AUC24hr). Meal: ~ 600 kcal, ~ 25 g fat.
c
Tecovirimat is metabolized by hydrolysis of the amide bond and glucuronidation. The following inactive
metabolites were detected in plasma: M4 (N-{3,5-dioxo-4-azatetracyclo[5.3.2.0{2,6}.0{8,10}]dodec-11-en-4yl}amine), M5 (3,5 dioxo-4-aminotetracyclo[5.3.2.0{2,6}.0{8,10}]dodec-11-ene), and TFMBA(4 (trifluoromethyl) benzoic acid)d
Uridine diphosphate (UDP)-glucuronosyl transferase (UGT) enzymeset½ value refers to mean terminal plasma half-life.
fSingle dose administration of [14C]-tecovirimat in mass balance study.
KEY: NA = Not Applicable or Not Available

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Comparison of Animal and Human PK Data to Support Effective Human Dose Selection
Because the effectiveness of TPOXX cannot be tested in humans, a comparison of tecovirimat
exposures achieved in healthy human subjects to those observed in animal models of
orthopoxvirus infection (nonhuman primates and rabbits infected with monkeypox virus andrabbitpox virus, respectively) in therapeutic efficacy studies was necessary to support the dosage
regimen of 600 mg every 12 hours for treatment of smallpox disease in humans. Humans
achieve greater systemic exposure (AUC, Cmax, and Cmin) of tecovirimat following a dose of
600 mg every 12 hours when compared to the therapeutic exposures in these animal models.
Specific Populations
No clinically significant differences in the pharmacokinetics of tecovirimat were observed basedon age, sex, ethnicity, renal impairment (based on estimated GFR), or hepatic impairment (Child
Pugh Scores A, B or C). At the 600 mg twice-daily oral dosage, tecovirimat exposure was
reduced in adult subjects weighing more than 120 kg compared to the exposures in adult subjects
weighing less than 120 kg. Specifically, in 34 adult subjects weighing more than 120 kg who
received 600 mg TPOXX orally every 12 hours, the observed mean steady state values of
AUC0-24hr, Cmax, and Ctrough were 19500 hr•ng/mL (CV: 23%), 1300 ng/mL (CV: 29%), and585 ng/mL (CV: 31%), respectively.
Pediatric PatientsTPOXX pharmacokinetics has not been evaluated in pediatric patients. The recommended
pediatric dosing regimen is expected to produce tecovirimat exposures that are comparable tothose in adult subjects based on a population pharmacokinetic modeling and simulation approach[see Dosage and Administration (2.2) and Use in Specific Populations (8.4)].
Hydroxypropyl-β-cyclodextrin, when administered intravenously, is eliminated throughglomerular filtration which may be reduced in pediatric patients with renal immaturity[see Warnings and Precautions (5.2) and Use in Specific Populations (8.4)].
Drug Interaction Studies
The effect of tecovirimat on the exposure of co-administered drugs are shown in Table 7.
Table 7:

Drug Interactions – Changes in Pharmacokinetic Parameters for
Co Administered Drug in the Presence of TPOXXa

Co-Administered
Drug

Dose of Co-Administered
Drug (mg)Mean Ratio (90% CI) of Co-Administered
Drug PK With/Without TPOXXNo Effect = 1.00
Cmax
AUC∞
1.87
1.73
Flurbiprofen +omeprazole 20 single dose
24
(1.51, 2.31)(1.36, 2.19)
omeprazole +midazolamb
0.61
0.68
midazolam 2 single dose
(0.54, 0.68)(0.63, 0.73)
1.27
1.29
Repaglinide
2 single dose30
(1.12, 1.44)(1.19, 1.40)
0.86
0.84
Bupropion
150 single dose
24
(0.79, 0.93)(0.78, 0.89)a
All interaction studies conducted in healthy volunteers with tecovirimat 600 mg twice daily (every 12 hours).
bComparison based on exposures when administered as flurbiprofen + omeprazole + midazolam.
N

15
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No pharmacokinetic changes were observed for the following drug when co-administered with
tecovirimat: flurbiprofen.
Cytochrome P450 (CYP) Enzymes: Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19,
and a weak inducer of CYP3A4. Tecovirimat is not an inhibitor or an inducer of CYP2B6 or
CYP2C9.
In Vitro Studies Where Drug Interaction Potential Was Not Further Evaluated Clinically
CYP Enzymes: Tecovirimat is not an inhibitor of CYP1A2, CYP2D6, CYP2E1 or CYP3A4, andis not an inducer of CYP1A2. Tecovirimat is not a substrate for CYP1A2, CYP2B6, CYP2C8,CYP2C9, CYP2C19, CYP2D6 or CYP3A4.
UGT Enzymes: Tecovirimat is a substrate of UGT1A1 and UGT1A4.
Transporter Systems: Tecovirimat inhibited Breast Cancer Resistance Protein (BCRP) in vitro.
Tecovirimat is not an inhibitor of P-glycoprotein (P-gp), organic anion transporting polypeptides
1B1 and 1B3 (OATP1B1 and OATP1B3), organic anion transporter 1 (OAT1), OAT3, andorganic cation transporter 2 (OCT2). Tecovirimat is not a substrate for P-gp, BCRP, OATP1B1,and OATP1B3.

12.4.

Microbiology

Mechanism of Action
Tecovirimat targets and inhibits the activity of the orthopoxvirus VP37 protein (encoded by andhighly conserved in all members of the orthopoxvirus genus) and blocks its interaction withcellular Rab9 GTPase and TIP47, which prevents the formation of egress competent enveloped
virions necessary for cell to cell and long-range dissemination of virus.
Activity in Cell Culture
In cell culture assays, the effective concentrations of tecovirimat resulting in a 50% reduction invirus induced cytopathic effect (EC50), were 0.016-0.067 μM, 0.014-0.039 µM, 0.015 µM, and
0.009 µM, for variola, monkeypox, rabbitpox, and vaccinia viruses, respectively. Ranges given
for variola and monkeypox viruses are reflective of results from multiple strains assayed.
Non-antagonistic antiviral activity of tecovirimat and brincidofovir against orthopoxviruses has
been demonstrated in cell culture and animal models.
Resistance
There are no known instances of naturally occurring tecovirimat resistant orthopoxviruses,
although tecovirimat resistance may develop under drug selection. Tecovirimat has a relatively
low resistance barrier, and certain amino acid substitutions in the target VP37 protein can confer
large reductions in tecovirimat antiviral activity. The possibility of resistance to tecovirimat
should be considered in patients who either fail to respond to therapy or who develop
recrudescence of disease after an initial period of responsiveness.

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Cross-resistance
Cross-resistance between tecovirimat and brincidofovir is not expected based on their distinct
mechanisms of action. Where tested, orthopoxvirus isolates resistant to cidofovir (the active
metabolite of brincidofovir) have not been resistant to tecovirimat. Likewise, orthopoxvirus
isolates resistant to tecovirimat retain their sensitivity to cidofovir.

13.

NONCLINICAL TOXICOLOGY

13.1.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis and Mutagenesis
Carcinogenicity studies have not been conducted with tecovirimat.
Tecovirimat was not genotoxic in in vitro or in vivo assays, including a bacterial reverse
mutation assay, a mammalian mutagenicity assay in mouse lymphoma L5178Y/TK± cells, and in
an in vivo mouse micronucleus study.
Impairment of Fertility
In a fertility and early embryonic development study in mice, no effects of tecovirimat on female
fertility were observed at tecovirimat exposures (AUC) approximately 24 times higher thanhuman exposure at the RHD. In male mice, decreased male fertility associated with testicular
toxicity (increased percent abnormal sperm and decreased sperm motility) was observed at
1,000 mg/kg/day (approximately 24 times the human exposure at the RHD).

13.2.

Animal Toxicology and/or Pharmacology

In a repeat-dose toxicology study in dogs, convulsions (tonic and clonic) were observed in one
animal within 6 hours of a single dose of 300 mg/kg (approximately 4 times higher than thehighest observed human exposure at the RHD based on Cmax). Electroencephalography (EEG)
findings in this animal were consistent with seizure activity during the observed convulsions.
Tremors, which were considered non-adverse, were observed at 100 mg/kg/dose (similar to thehighest observed human exposure at the RHD based on Cmax), although no convulsions or EEG
findings were observed at this dose.

14.

CLINICAL STUDIES

Overview
The effectiveness of TPOXX for treatment of smallpox disease has not been determined inhumans 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. Therefore, theeffectiveness of TPOXX for treatment of smallpox disease was established based on results ofadequate and well-controlled animal efficacy studies of non-human primates and rabbits infectedwith non-variola orthopoxviruses. Survival rates observed in the animal studies may not be
predictive of survival rates in clinical practice.

17
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Study Design
Efficacy studies were conducted in cynomolgus macaques infected with monkeypox virus, and
New Zealand white (NZW) rabbits infected with rabbitpox virus. The primary efficacy endpoint
for these studies was survival. In non-human primate studies, cynomolgus macaques were
lethally challenged intravenously with 5 x 107 plaque-forming units of monkeypox virus;
tecovirimat was administered orally once daily at a dose level of 10 mg/kg for 14 days, startingat Day 4, 5 or 6 post-challenge. In rabbit studies, NZW rabbits were lethally challenged
intradermally with 1,000 plaque-forming units of rabbitpox virus; tecovirimat was administeredorally once daily for 14 days at a dose level of 40 mg/kg, starting at Day 4 post-challenge.
The timing of tecovirimat dosing in these studies was intended to assess efficacy when treatment
is initiated after animals have developed clinical signs of disease, specifically dermal pox lesions
in cynomolgus macaques, and fever in rabbits. Clinical signs of disease were evident in someanimals at Day 2-3 post-challenge but were evident in all animals by Day 4 post-challenge.
Survival was monitored for 3-6 times the mean time to death for untreated animals in eachmodel.
Study Results
Treatment with tecovirimat for 14 days resulted in statistically significant improvement insurvival relative to placebo, except when given to cynomolgus macaques starting at Day 6
post-challenge (Table 8).
Table 8:Survival Rates in Tecovirimat Treatment Studies in Cynomolgus Macaquesand NZW Rabbits Exhibiting Clinical Signs of Orthopoxvirus Disease
Treatment
Initiationa

Cynomolgus Macaques
Study 1Day 4
Study 2Day 4
Study 3
Day 4
Day 5
Day 6
NZW Rabbits
Study 4Day 4
Study 5
Day 4

Survival Percentage(No. survived/n)
PlaceboTecovirimat

p-valueb

Survival Rate
Differencec(95% CI)d0% (0/7)
0% (0/6)
0% (0/3)

80% (4/5)
100% (6/6)
83% (5/6)
83% (5/6)
50% (3/6)

0.00380.00020.01510.01510.123180% (20.8%, 99.5%)
100% (47.1%, 100%)83% (7.5%, 99.6%)
83% (7.5%, 99.6%)
50% (-28.3%, 90.2%)

0% (0/10)NAe

90% (9/10)
88% (7/8)< 0.0001
NA

90% (50.3%, 99.8%)NAaDay post-challenge tecovirimat treatment was initiatedp-value is from 1-sided Boschloo Test (with Berger-Boos modification of gamma = 0.000001) compared to placebocSurvival percentage in tecovirimat treated animals minus survival percentage in placebo treated animalsdExact 95% confidence interval based on the score statistic of difference in survival ratese
A placebo control group was not included in this study.
KEY: NA = Not Applicableb18
Reference ID: 4985981

16.

HOW SUPPLIED/STORAGE AND HANDLINGTPOXX Capsule
How Supplied
Each TPOXX capsule contains 200 mg of tecovirimat. 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 bottle contains 42 capsules (NDC 50072-200-42) with an induction seal
and child-resistant cap.
Storage and HandlingStore capsules in the original bottle at 20°C to 25°C (68°F to 77°F); excursions permitted 15°C
to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
TPOXX Injection
How Supplied
TPOXX injection is supplied in a 30 mL single-dose vial as a clear, colorless to pale yellow
solution for intravenous administration containing 200 mg/20 mL (10 mg/mL) of tecovirimat(NDC 50072-010-30). This solution is intended for dilution with either 0.9% (w/v) sodium
chloride injection or 5% (w/v) dextrose injection solution. The vial stopper is not made withnatural rubber latex. The vials are packed in cartons of seven vials. Short-term (up to 24 hours)
storage and handling at an ambient temperature is acceptable.
Storage and HandlingStore TPOXX injection in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.
The diluted solution(s) of TPOXX injection with either 0.9% (w/v) sodium chloride (normal
saline) or 5% (w/v) dextrose solution should be used within 4 hours of preparation if stored atroom temperature or within 24 hours of preparation if stored at 2°C to 8°C [see Dosage andAdministration (2.5)].

19
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17.

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information andInstructions for Use).
Efficacy Based on Animal Models Alone
Inform patients that the efficacy of TPOXX is based solely on efficacy studies demonstrating asurvival benefit in animals and that the effectiveness of TPOXX has not been tested in humans
with smallpox disease [see Clinical Studies (14)].
Important Dosage and Administration Information
Advise patients to take TPOXX capsules as directed within 30 minutes of eating a full meal
containing moderate or high fat with 6-8 oz. of water [see Clinical Pharmacology (12.3)].
Inform patients to take TPOXX for the entire duration without missing or skipping a dose[see Dosage and Administration (2)].
Inform patients who cannot swallow capsules to refer to the Instructions for Use [see Dosage
and Administration (2)].
Drug Interactions
Inform patients that TPOXX may interact with other drugs. Advise patients to report to theirhealthcare provider the use of other prescription drugs. Co-administration of TPOXX withrepaglinide may cause hypoglycemia [see Warnings and Precautions (5.1) and Drug
Interactions (7.2)].
TPOXX injection: Hydroxypropyl-β-cyclodextrin, a required component of TPOXX injection,is eliminated through glomerular filtration. Therefore, in patients with severe renal impairment(defined as creatinine clearance below 30 mL/min), the use of TPOXX injection iscontraindicated. [see Contraindications (4)]. In patients with mild (defined as creatinine
clearance 60-89 mL/min) and moderate (defined as creatinine clearance 30-59 mL/min) renal
impairment, TPOXX injection should be used with caution [see Warnings and Precautions (5.2)
and Use in Specific Populations (8.6)].
Lactation
Instruct individuals with smallpox not to breastfeed their infant because of the risk of passing
variola virus to the breastfed infant [see Use in Specific Populations (8.2)].
TPOXX capsules manufactured by:
Catalent Pharma Solutions, LLC
1100 Enterprise Drive
Winchester, KY 40391

20
Reference ID: 4985981

TPOXX injection manufactured by:
Patheon Manufacturing Services LLC
5900 Martin Luther King Jr. Highway
Greenville, NC 27834
Distributed by:
SIGA Technologies, Inc.
4575 SW Research Way, Suite 110
Corvallis, OR 97333

21
Reference ID: 4985981

PATIENT INFORMATIONTPOXX (Tē-Pox or Tee-pahx)(tecovirimat)
capsules, for oral use®

TPOXX® (Tē-Pox or Tee-pahx)(tecovirimat)
injection, for intravenous use

What is TPOXX?
TPOXX is a prescription medicine used to treat smallpox disease caused by a type of virus called variola virus inadults and children who weigh at least 7 pounds (3 kg).
•

The effectiveness of TPOXX has been studied only in animals with orthopoxvirus diseases. There have been no
human studies in people who have smallpox disease.

•

The safety of TPOXX was studied in adults. There have been no studies of TPOXX in children 17 years of age andyounger.

•

TPOXX may not work well in people who have a weakened immune system (immunocompromised).

Who should not receive TPOXX injection?
Do not receive TPOXX injection if you or your child have severe kidney problems TPOXX injection contains an
ingredient called hydroxypropyl β-cyclodextrin which is cleared from your body through the kidneys. Tell yourhealthcare provider if you or your child have kidney problems because receiving TPOXX injection may not be right foryou or your child.
Before taking or receiving TPOXX, tell your healthcare provider about all of your or your child’s medical
conditions, including if you or your child:•
have diabetes.
•

have kidney problems.

•

are pregnant or plan to become pregnant. It is not known if TPOXX can harm the unborn baby. Tell yourhealthcare provider if you or your child become pregnant during treatment with TPOXX.

are breastfeeding or plan to breastfeed. It is not known if TPOXX passes into your breast milk. You should notbreastfeed during treatment with TPOXX.
o
You should not breastfeed if you have smallpox because of the risk of passing variola virus to the breastfed
infant.
oTalk to your healthcare provider about the best way to feed the baby during treatment with TPOXX.
Tell your healthcare provider about all of the medicines you or your child take, including prescription andover-the-counter medicines, vitamins, and herbal supplements.
Using TPOXX with certain other medicines may affect each other causing possible serious side effects. You can ask
your healthcare provider or pharmacist for a list of medications that interact with TPOXX.
•

Especially tell your healthcare provider if you take a medicine used to treat type 2 diabetes called repaglinide.
Know the medicines you or your child take. Keep a list of your medicines to show your healthcare provider andpharmacist when you get a new medicine. Do not start taking a new medicine without telling your healthcare
provider. Your healthcare provider can tell you if it is safe to take TPOXX with other medicines.
How should I take TPOXX?
•
Stay under the care of your healthcare provider during treatment with TPOXX.
TPOXX capsules:•

Take TPOXX capsules exactly as your healthcare provider tells you. Do not change the dose or stop taking
TPOXX without talking to your healthcare provider.

•

For adults and children who weigh at least 40 kg and less than 120 kg, take 3 capsules of TPOXX 2 times aday (every 12 hours) by mouth for 14 days.

•

For adults and children who weigh at least 120 kg, take 3 capsules of TPOXX 3 times a day (every 8 hours)by mouth for 14 days.

•

TPOXX should be taken within 30 minutes after eating a full meal of moderate or high fat (approximately
600 calories and 25 grams of fat). Swallow capsules whole with 6 to 8 ounces of water. Talk to your healthcare
provider about examples of foods that you can eat that contain about 25 grams of fat. Always take TPOXX with
food.

•

See the “Instructions for Use” that comes with your TPOXX capsules for instructions on how to prepare and takea dose of TPOXX if:

Reference ID: 4985981

o your child weighs less than 88 pounds (40 kg), oro you or your child have trouble swallowing TPOXX capsules.

• It is important to take TPOXX for the full 14 day course of treatment. Do not miss or skip a dose of TPOXX.
• If you miss an oral dose of TPOXX, you should take the dose as soon as possible and anytime up to 8 hours
before the next scheduled dose. If less than 8 hours remain before the next scheduled dose, do not take themissed dose, and take your next dose as scheduled.
• If you take too much TPOXX, call your healthcare provider or go to the nearest hospital emergency room rightaway.
TPOXX Injection for Intravenous Infusion (IV)TPOXX injection is given to you or your child by intravenous (IV) infusion into a vein slowly over 6 hours using an
infusion pump by a health care provider.
What are the possible side effects of TPOXX?
TPOXX may cause serious side effects, including:• Low blood sugar (hypoglycemia). Low blood sugar can happen when TPOXX is taken or received withrepaglinide, a medicine used to treat type 2 diabetes. Tell your healthcare provider if you get any of the following
symptoms of low blood sugar:• headache• dizziness• weakness• drowsiness• confusion• fast heartbeat• hunger• sweating• irritability• feeling jittery or shaky
The most common side effects of TPOXX capsules include:• headache• stomach pain
• nausea• vomiting
The most common side effects of TPOXX injection include:• reactions at the site of your IV infusion
These are not all the possible side effects of TPOXX.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088
How should I store TPOXX capsules?
• Store TPOXX at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep TPOXX in its original container.
Keep TPOXX and all other medicines out of the reach of children.
General information about the safe and effective use of TPOXX.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use
TPOXX for a condition for which it was not prescribed. Do not give TPOXX to other people, even if they have thesame symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for
information about TPOXX that is written for health professionals.
What are the ingredients in TPOXX?
TPOXX capsules: 200 mg
Active ingredient: tecovirimat
Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl methyl cellulose, lactose
monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The capsule shell is madeof gelatin, FD&C blue No.1, FD&C red No.3, FD&C yellow No.6, and titanium dioxide.
TPOXX injection: 200 mg in each 20 mL vial
Active ingredient: tecovirimat
Inactive ingredients: hydroxypropyl β-cyclodextrin and water for injection.
TPOXX capsules manufactured by:
Catalent Pharma Solutions,1100 Enterprise Drive,

Reference ID: 4985981

Winchester, KY 40391
TPOXX injection manufactured by:
Patheon Manufacturing Services LLC,
5900 Martin Luther King Jr. Highway,
Greenville, NC 27834
Distributed By:
SIGA Technologies, Inc.
4575 SW Research Way, Suite 110
Corvallis, OR 97333
For more information, go to www.SIGA.com or call 1-888-899-3472.
This Patient Information has been approved by the U.S. Food and Drug Administration.

Reference ID: 4985981

Issued: 05/2022