teprotumumab (Rx)

>10%

Muscle spasms (25%)

Nausea (17%)

Alopecia (13%)

Diarrhea (12%)

Fatigue (12%)

1-10%

Hyperglycemia (10%)

Hearing impairment (10%)

Dysgeusia (8%)

Headache (8%)

Dry skin (8%)

Postmarketing Reports

Exacerbation of preexisting inflammatory bowel disease

Infusion reactions

Metabolism and nutrition disorders: Diabetic ketoacidosis, hyperosmolar hyperglycemic state (HHS)

Otologic: Severe hearing impairment including hearing loss, which may be permanent

Contraindications

None

Cautions

Infusion reactions may occur; if an infusion reaction occurs, interrupt or slow infusion rate and use appropriate medical management

May cause exacerbation of preexisting inflammatory bowel disease (IBD); monitor patients with preexisting IBD for flare of disease; discontinue treatment if IBD worsens

Hyperglycemia reported; assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to monitor while on treatment; ensure patients with hyperglycemia or pre-existing diabetes are under appropriate glycemic control before and while receiving therapy

May cause severe hearing impairment including hearing loss, which in some cases may be permanent; assess patients’ hearing before, during, and after treatment and consider benefit-risk of treatment with patients

Pregnancy

Based on findings in animals and its mechanism of action, fetal harm may occur when administered to a pregnant woman

Adequate and well-controlled studies have not been conducted in pregnant women

Data are insufficient with use in pregnant women to inform any drug-associated risks for adverse developmental outcomes

Animal data

• In utero teprotumumab exposure in cynomolgus monkeys dosed once weekly with teprotumumab throughout pregnancy resulted in external and skeletal abnormalities
• Teprotumumab exposure may lead to an increase in fetal loss; therefore, do not use during pregnancy
• If patient becomes pregnant during treatment, discontinue treatment and advise patient of the potential risk to the fetus

Contraception

• Advise females of reproductive potential to use effective contraception before initiation, during treatment, and for 6 months following the last dose

Lactation

There is no information regarding the presence of teprotumumab in human milk, the effects on the breastfed infant, or the effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Monoclonal antibody that binds insulin-like growth factor-1 receptor (IGF-1R)

Mechanism of action for thyroid eye disease has not been fully characterized

Teprotumumab-trbw binds to IGF-1R and blocks its activation and signaling

Absorption

Peak plasma concentration: 632 mcg/mL

Trough plasma concentration: 176 mcg/mL

AUC: 138 mg⋅hr/mL

Distribution

Vd: 3.26 L (central); 4.32 L (peripheral)

Metabolism

Metabolism has not been fully characterized

However, teprotumumab-trbw is expected to undergo metabolism via proteolysis

Elimination

Clearance: 0.27 L/day

Half-life: 20 days

IV Incompatibilities

Do not infuse concomitantly with other agents

IV Compatibilities

0.9% NaCl

No incompatibilities with polyethylene (PE), polyvinyl chloride (PVC), polyurethane (PUR), or polyolefin (PO) bags, and IV administration sets have been observed

IV Preparation

Reconstitution

• Calculate dose and determine number of vials needed; each vial contains 500 mg of teprotumumab antibody
• Reconstitute each vial with 10 mL of sterile water for injection; do not direct the stream of diluent onto the lyophilized powder, which has a cake-like appearance
• Do not shake; gently swirl solution by rotating the vial until powder is dissolved
• Reconstituted solution has a volume of 10.5 mL (final concentration is 47.6 mg/mL); withdraw 10.5 mL of reconstituted solution to obtain 500 mg

Dilution

• Further dilute in 0.9% NaCl
• To maintain a constant volume in the infusion bag, remove the volume equivalent to the amount of the reconstituted to be placed into the infusion bag
• Withdraw required volume from the reconstituted vial(s) and transfer into an IV bag containing 0.9% NaCl to prepare a diluted solution with a total volume of 100 mL (for less than an 1800-mg dose) or 250 mL (for 1800-mg and greater dose)
• Mix diluted solution by gentle inversion; do not shake

• Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit; solution should appear as a colorless or slightly brown, clear-to-opalescent solution that is free of foreign particulate matter

• Discard solution if any particulate matter or discoloration is observed

• Discard vial(s) and all unused contents.

IV Administration

First 2 infusions: Infuse over 90 min

Subsequent infusions: If well tolerated, may reduce infusion time to 60 min; if not well tolerated, keep infusion time at 90 min

Do not administer as an IV push or bolus

Storage

Protect from light

Do not freeze

Unused vials: Refrigerate at 2-8ºC (36-46ºF) in original carton until time of use

Reconstituted vials and diluted solutions

• Store at room temperature (20-25ºC [68-77ºF]) for up to 4 hr OR
• Refrigerate at 2-8ºC (36-46ºF) for up to 48 hr