Increlex

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Increlex, there are no specific foods that you must exclude from your diet when receiving this medication.

If you take too much Increlex, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Increlex is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Your child should not use mecasermin if he or she is allergic to it, or if:

• the child has cancer; or

• the child has finished growing and his or her bone growth plates are closed.

To make sure mecasermin is safe for your child, tell the doctor if the child has:

• diabetes;

• kidney disease;

• liver disease; or

• a curved spine (scoliosis).

It is not known whether this medicine will harm an unborn baby if used during pregnancy.

It is not known whether mecasermin passes into breast milk or if it could harm a nursing baby.

Mecasermin is not approved for use by anyone younger than 2 years old.

Absorption

Bioavailability

Following sub-Q administration in healthy individuals, bioavailability is approximately 100%.1 16 25 Bioavailability in individuals with IGF-I deficiency not determined.1 25

In individuals with severe IGF-I deficiency, serum concentrations of IGF-I were very low prior to mecasermin administration.11 Following administration of a single dose (0.12 mg/kg) in these individuals, average peak plasma concentrations attained at 2 hours were below normal or in the low-normal range.1 11 13 16 25

Distribution

Extent

Tissue availability of free IGF-I determined by presence of 6 IGF binding proteins (IGFBPs) in the blood.1 8 11 IGFBPs, particularly IGFBP-3, limit the extent of distribution.11

Not known whether mecasermin is distributed into milk.1

Plasma Protein Binding

>99% of circulating IGF-I bound to IGFBPs,1 8 with >80% bound as a complex with IGFBP-3 and an acid labile subunit.1 8 25 Plasma concentrations of IGFBP-3 and acid labile subunit are reduced in patients with severe primary IGFD compared with healthy individuals, resulting in greater drug clearance.1 3 14 15 (See Half-life under Pharmacokinetics.)

Elimination

Metabolism

Mecasermin and endogenous IGF-I are metabolized by lysosomal enzymes principally in the liver and kidneys to amino acids.1 11 16 21 25

Elimination Route

Excreted principally in urine.16 21 Presumably less than 0.1% is excreted in urine as unchanged drug based on studies with endogenous IGF-I.21

Half-life

Terminal half-life averages 5.8 hours in children with severe primary IGFD1 11 16 25 and 19.2 hours in healthy individuals.1 11 16

Clearance of free IGF-I occurs at a faster rate than IGF-I bound to IGFBPs; therefore, patients with severe primary IGFD have increased clearance and shorter half-life of IGF-I compared with healthy individuals.1 3 11 14 (See Plasma Protein Binding under Pharmacokinetics.)

• Provide copy of manufacturer’s patient information to the patient and/or patient’s parent or guardian and advise of the importance of reading this information each time a new or refill prescription is dispensed.5

• Importance of advising patients and/or patient’s parent or guardian about safe administration of the drug and proper disposal of used needles and syringes.1 5

• Importance of administering the drug ≤20 minutes before or after a meal or snack.1 5 Advise patient and/or patient’s parent or guardian not to administer the drug if the meal or snack is omitted prior to administration and not to make up the missed dose.1 5

• Importance of proper glucose monitoring and how to recognize signs and symptoms of hypoglycemia.1 5 Advise patient and/or patient’s parent or guardian to always keep a source of carbohydrates (e.g., orange juice, candy) available in case hypoglycemia occurs.1 5 For severe cases, advise patient and/or patient’s parent or guardian on the proper use of glucagon injection.1 5

• Importance of avoiding high-risk activities (e.g., driving) within 2–3 hours following drug administration, particularly after therapy initiation, until a well-tolerated dosage established.1 5

• Importance of advising patients and/or patient’s parent or guardian of possible allergic reactions.1 5 Importance of discontinuing therapy and contacting a clinician promptly if allergic reactions (e.g., rash, hives, breathing problems, shock) occur.1 5

• Advise patient and/or patient’s parent or guardian that the drug should not be used if the child has finished growing (i.e., bone growth plates are closed), has cancer, or has causes of growth failure other than primary IGF-I deficiency.1 5

• Importance of informing clinicians if signs and symptoms of enlarged tonsils (e.g., snoring, breathing or swallowing problems, sleep disorders, hearing disorders, fluid in middle ear) occur.1 5

• Importance of informing clinicians if signs and symptoms of increased pressure in the brain (e.g., headache, nausea, vomiting, vision disorders) occur.1 5 Advise patient that funduscopic examination is recommended at treatment initiation and periodically thereafter.1

• Importance of informing clinicians immediately if the patient develops a limp or hip or knee pain, since these may be signs of a slipped capital femoral epiphysis (a condition that occurs when the top of the femur slips apart from the ball of the hip joint).5

• Risk of worsening scoliosis caused by rapid growth.1 5 Importance of clinicians evaluating patients with scoliosis for increased curvature of the spine during therapy.1 5

• Importance of patients informing clinicians if they are or plan to become pregnant or plan to breast-feed.5

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., insulin, other antidiabetic agents), vitamins, and herbal supplements, as well as any concomitant illnesses (e.g., diabetes mellitus, kidney or liver disease, curved spine).1 5

• Importance of informing patients and/or patient’s parent or guardian of other important precautionary information.1 (See Cautions.)

In the U.S.

• Increlex
• Iplex

Available Dosage Forms:

• Solution

Therapeutic Class: Endocrine-Metabolic Agent

This section provides information on the proper use of a number of products that contain mecasermin. It may not be specific to Increlex. Please read with care.

Your doctor will prescribe your child's exact dose and tell you how often it should be given. This medicine is given as a shot under your child's skin. This medicine must not be injected into a vein or muscle.

Some medicines given by injection may sometimes be given at home to patients who do not need to be in the hospital. If you are using this medicine at home, your doctor will teach you how to prepare and inject the medicine. You will have a chance to practice preparing and injecting it. Be sure that you understand exactly how the medicine is to be prepared and injected.

It is important to read the patient information and instructions for use, if provided with your medicine, each time your prescription is filled.

This medicine must be taken 20 minutes before or 20 minutes after a snack or meal. Never let your child skip a meal once your child received this medicine.

Use a new needle and syringe each time you inject the medicine to your child.

It is important to follow any instructions from your doctor about the careful selection and rotation of injection sites (e.g., upper arms, thighs, buttocks, or abdomen) on your body. This will help to prevent skin problems.

Do not use the medicine if it looks cloudy or has particles in it.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For treatment of growth failure caused by IGF-1 deficiency:
    • Children 2 years of age and older—Dose is based on body weight and must be determined by your doctor. The starting dose is 0.04 to 0.08 milligram (mg) per kg (0.018 to 0.036 mg per lb) of body weight injected under the skin two times a day. Your doctor may then increase the dose, if needed.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store in the refrigerator. Do not freeze.

You may keep the opened vial in the refrigerator. Use it within 30 days after opening. Throw away any unused medicine after 30 days. Do not freeze the solution and protect it from direct heat and light.

Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

• If your child has an allergy to Increlex (mecasermin injection) or any part of this medicine.
• If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If your child has cancer.
• If your child's bones are no longer growing (closed epiphyses).

This is not a list of all drugs or health problems that interact with Increlex.

Tell the doctor and pharmacist about all of your child's drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this medicine with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child's doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Change in eyesight, eye pain, or very bad eye irritation.
• Snoring.
• Breathing problems during sleep (sleep apnea).
• Larger tonsils.
• Ear pain.
• Very bad headache.
• Very upset stomach or throwing up.
• Hip or knee pain, or a limp.
• Seizures.
• Low blood sugar may occur. Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call the doctor right away if any of these signs occur. Follow what you have been told to do if low blood sugar occurs. This may include taking glucose tablets, liquid glucose, or some fruit juices.

Treatment of acute overdose should be directed at reversing hypoglycemia. Oral glucose or food should be consumed. If the overdose results in loss of consciousness, intravenous glucose or parenteral glucagon may be required to reverse the hypoglycemic effects.

A small number of overdose cases have been reported in the post-marketing experience. In one case of acute overdose, a 3-year old patient experienced hypoglycemia after receiving one 4 mg dose of Increlex® (a 10-fold increase beyond the prescribed dose). The event resolved following treatment with IV glucose.

Long term overdosage with Increlex® may result in signs and symptoms of acromegaly.

NDC-15054-1040-5 Increlex® is supplied as a 10 mg per mL sterile solution in multiple dose glass vials (40 mg per vial).

Before Opening – Vials of Increlex® are stable when refrigerated [2º to 8ºC (35º to 46ºF)]. Avoid freezing the vials of Increlex®. Protect from direct light. Expiration dates are stated on the labels.

After Opening – Vials of Increlex® are stable for 30 days after initial vial entry when stored at 2º to 8ºC (35º to 46ºF). Avoid freezing the vials of Increlex®. Protect from direct light.

Vial contents should be clear without particulate matter. If the solution is cloudy or contains particulate matter, the contents must not be injected. Increlex® should not be used after its expiration date. Keep refrigerated and use within 30 days of initial vial entry. Remaining unused material should be discarded.

NDC 15054-1040-5
One multi-use vial

Rx only

Increlex®
(mecasermin [rDNA origin]
injection)

40 mg/4 mL
(10 mg/mL)

For subcutaneous use only

Net wt. 40 mg

TN5UC-01

Your child should not use Increlex if he or she is allergic to mecasermin, or if:

• the child has cancer; or

• the child has finished growing and his or her bone growth plates are closed.

To make sure Increlex is safe for your, tell the doctor if your child has:

• diabetes;

• kidney disease;

• liver disease; or

• a curved spine (scoliosis).

It is not known whether Increlex will harm an unborn baby if used during pregnancy.

It is not known whether mecasermin passes into breast milk or if it could harm a nursing baby.

Increlex is not approved for use by anyone younger than 2 years old.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of mecasermin can cause severe hypoglycemia.

Symptoms of severe hypoglycemia may include extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, or seizure (convulsions).

Long term use of high mecasermin doses can lead to unusual or excessive growth in any part of the body.

Get emergency medical help if your child has signs of an allergic reaction to Increlex: hives; difficult breathing; swelling of your child's face, lips, tongue, or throat.

Call your doctor at once if your child has:

• pain in the hip or knee, walking with a limp;

• low blood sugar - headache, hunger, weakness, sweating, confusion, irritability, dizziness, fast heart rate, or feeling jittery;

• swollen tonsils - snoring, breathing problems during sleep, pain or fullness in the ear, hearing problems; or

• increased pressure inside the skull - headache with vision problems, nausea, pain behind the eyes.

Common Increlex side effects may include:

• low blood sugar;

• swollen tonsils; or

• an allergic reaction.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.