Mecasermine
Generic name
Mecasermine
Brand name
ATC Code
H01AC03
- Dosages
- Side effects in children
- Warnings & precautions in children
- Contra-indications in children
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Interactions - PK
- Renal impairment
- References
Pharmacokinetics in children
The mean terminal t1/2 of total IGF-1 following a single subcutaneous administration of 0.12 mg/kg to three pediatric subjects with severe primary IGFD has been estimated to be 5.8 hours (SmPC).
Another case describes a t1/2 of 1.3-3 h following a single subcutaneous injection of 0.1 and 0.2 mg/kg (on separate days) in a pediatric patient (age 3 years and 9 months) with Rabson-Mendall syndrome (Longo 2001).
In the study of Khwaja 2014 the following noncompartmental PK parameters (means ±SD) were found during 4 weeks of therapy with SC injections in 12 patients with MECP2 mutations (9 of whom had Rett syndrome) aged 2-10 years:
| 40 μg/kg BID | 80 μg/kg BID | 120 μg/kg BID | ||
| Week 1 | Week 2 | Week 3 | Week 4 | |
| Tmax (h) | 3,4 ± 0,5 | 2,0 ± 0,3 | 1,9 ± 0,2 | 1,5 ± 0,2 |
| Cmax (ng/ml) | 234,9 ± 16,6 | 407,9 ± 42,0 | 458,5± 29,5 | 434,1 ± 29,3 |
| T1/2 (h) | 18,2 ± 11,3 | 14,6 ± 1,5 | 14,0 ± 2,0 | 12,9 ± 1,7 |
This study also concluded that mecasermin follows nonlinear kinetics, with greater distribution in the peripheral compartment
| Vd central compartment (mean ± SE) | 7,71 ± 0,78 L |
| Vd peripheral compartment (mean ± SE) | 33,5 ± 16 L |
| Intercompartimentale klaring (mean ± SE) | 0,38 ± 0,048 L/h |
dose recommendation of formulary compared to licensed use (on-label versus off-label)
No information is present at this moment.
Available formulations
No information is present at this moment.
Dosages
| Growth disorders with severe primary insulin-like growth factor 1 deficiency (IGFD). |
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| Severe insulin resistance syndrome |
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Renal impaiment in children > 3 months
No information available on dose adjustment in renal impairment.
The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here
Side effects in children
Very common (> 10%): hypoglycemia. Headache. Otitis media. Vomiting, abdominal pain. Joint pain, pain in limbs. Hypertrophy at the injection site, bruising at the injection site.
Common (1-10%): thymus hypertrophy. Hypoglycemic insult, hyperglycemia. Convulsions, dizziness, tremor. Papilledema. Hypoacusis, ear pain, fluid in the middle ear. Heart murmur, tachycardia. Tonsil hypertrophy (especially in the first 1–2 years), adenoid hypertrophy, sleep apnea syndrome, snoring. Skin hypertrophy, abnormal hair structure. Scoliosis, muscle pain. Melanocytic nevus. Gynecomastia. Pain, irritation, erythema, induration, or hemorrhage at the injection site.
Sometimes (0.1–1%): depression, nervousness. Benign intracranial hypertension. Cardiomegaly, ventricular hypertrophy, mitral or tricuspid valve insufficiency. Skin rash or swelling at the injection site, lipohypertrophy. Weight gain.
The following have also been reported: systemic hypersensitivity (anaphylaxis, generalized urticaria, angioedema, dyspnea), local allergic reactions at the injection site (itching, urticaria). Alopecia. Various benign and malignant neoplasms (including rare malignancies, which are not usually observed in children).
[SmPC]
Literature [Plamper 2018]:
Common: Paresthesia
Rare: swelling of the parotid gland, facial paralysis, (worsening of) retinopathy, fluid accumulation/edema, mastitis, and endometrial cancer.
The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here
Contra-indications in children
- Active or suspected neoplasia
- History or condition leading to an increased risk of benign or malignant neoplasia.
The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here
Warnings & precautions in children
The diagnosis of severe primary IGFD is defined by a height standard deviation score ≤ –3.0, a basal IGF-1 level below the 2.5th percentile for age and sex, adequate growth hormone, exclusion of secondary forms (such as malnutrition, hypopituitarism, hypothyroidism, chronic treatment with pharmacological doses of anti-inflammatory steroids). Confirm the diagnosis if necessary by means of an IGF-1 generation test.
The risk of benign and malignant neoplasia increases with treatment with mecasermin. IGF-1 may play a role in malignancies in all organs and tissues. Be alert to symptoms that may indicate neoplasia and discontinue treatment in such cases.
Perform an echocardiogram prior to and after discontinuation of treatment. Regularly monitor patients with abnormalities or cardiovascular symptoms by echocardiography.
Mecarsimine may cause hypoglycemia. Use caution in young children, children with a history of hypoglycemia, or children with irregular eating patterns. Avoid risky activities, especially at the start of treatment and for 2–3 hours after administration. Patients with a history of severe hypoglycemia should have glucagon available.
It may be necessary to reduce the dose of insulin and/or other glucose-lowering medicines in diabetic patients using this medicine.
Intracranial hypertension has been reported. Fundoscopic examination is recommended at the start of and during treatment, as well as in the event of clinical symptoms such as visual changes, headache, nausea, and/or vomiting.
Hypertrophy of lymphoid tissue (e.g., the tonsils) has been reported. Check periodically for complications such as snoring, sleep apnea, and chronic middle ear infection.
Femoral epiphysiolysis and progression of scoliosis may occur in patients who are growing rapidly. During treatment, check for symptoms such as limping and pain in the hips or knees.
Discontinue treatment immediately in case of allergic reactions. In case of allergic reaction, unexpectedly high IGF-1 blood levels, or lack of growth response, perform an antibody test.
If no response has occurred after one year, reconsider treatment.
Discontinue treatment when the epiphyseal plates are closed.
Interactions
The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here
ANTERIOR PITUITARY LOBE HORMONES AND ANALOGUES
This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.
| ACTH | ||
|---|---|---|
| H01AA02 | ||
| Somatropin and somatropin agonists | ||
|---|---|---|
| H01AC09 | ||
| H01AC07 | ||
| H01AC08 | ||
| H01AC01 | ||
References
- Ipsen Pharma, SmPC Increlex (EU/1/07/402/001) Rev 26; 06-01-2025, www.ema.europa.eu
- Ipsen Pharma GmbH, Rote-Hand-Brief: INCRELEX (Mecasermin): Risiko für gutartige und bösartige Neoplasien, 02/12/2019
- Khwaja OS, et al., Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome., Proc Natl Acad Sci U S A, 2014, 111(12), 4596-601
- Longo N, et al., Decreased half-life of insulin-like growth factor I in Rabson-Mendenhall syndrome., J Inherit Metab Dis, 2001, 24(5), 546-50
- Plamper M, et al 2018;, Mecasermin in Insulin Receptor-Related Severe Insulin Resistance Syndromes: Case Report and Review of the Literature., Int J Mol Sci., 2018, 19(5)
Changes
Therapeutic Drug Monitoring
Overdose
