Methimazole (Tapazole) Hair and Skin Changes: What Patients and Clinicians Need to Know

At a glance

• Drug form / oral methimazole tablets; the Tapazole brand is listed as discontinued [1][2]
• Hair loss / 'abnormal loss of hair' among minor adverse reactions [1]
• Skin reactions / rash, urticaria, pruritus and skin pigmentation among minor reactions [1]
• Vasculitis warning / can include leukocytoclastic cutaneous vasculitis and severe organ complications [1]
• ANCA / most reported vasculitis cases were ANCA-positive [1]
• Pregnancy skin defect / aplasia cutis reported in first-trimester exposed infants [1][3]
• Frequency / no incidence figure in the label for rash or hair loss [1]

What hair loss does the label list?

The FDA prescribing information for generic methimazole tablets lists 'abnormal loss of hair' in the minor adverse reactions section, together with skin rash, urticaria, pruritus and skin pigmentation [1]. The label does not name a type of alopecia, describe a follicle mechanism, or give a typical onset or recovery time for hair loss [1].

What skin reactions are listed?

Skin rash, urticaria, pruritus and skin pigmentation are in the label's minor adverse reactions list [1]. The label says major adverse reactions occur with much less frequency than minor ones; agranulocytosis, aplastic anemia and hepatitis are grouped with the major reactions [1].

Itching also appears in the liver toxicity warning: the label names pruritus as a symptom that should prompt liver tests, along with anorexia and right upper quadrant pain [1]. The label says treatment should be discontinued promptly for clinically significant liver abnormality, including transaminases above 3 times the upper limit of normal [1].

What is the vasculitis warning?

The label warns that vasculitis with severe complications has been reported [1]. Cases include leukocytoclastic cutaneous vasculitis, acute kidney injury and glomerulonephritis, alveolar/pulmonary hemorrhage, CNS vasculitis and neuropathy, and most were associated with ANCA-positive vasculitis [1].

The label says some cases resolved or improved with drug discontinuation, while more severe cases required corticosteroids, immunosuppressant therapy or plasmapheresis [1]. If vasculitis is suspected, the label directs discontinuation of therapy and appropriate intervention [1].

The label also lists rash, blood in urine or reduced urine output, shortness of breath and coughing blood among the signs to report for possible vasculitis [1].

Does a skin eruption change blood-count monitoring?

The agranulocytosis warning tells patients to report fever or sore throat immediately [1]. It also says to obtain white-cell and differential counts if sore throat, skin eruptions, fever, headache or malaise appear [1].

What about pregnancy and aplasia cutis?

First-trimester methimazole exposure can cause fetal harm, and the label lists rare congenital defects including aplasia cutis, craniofacial malformations, gastrointestinal malformations, omphalocele and omphalomesenteric duct abnormalities [1]. The label says it may be appropriate to use other agents in pregnant women who need treatment and, if methimazole is used, to give the lowest possible dose [1].

In a study of 6,744 women with Graves' disease whose pregnancy outcomes were known (5,967 live births), major anomalies occurred in 4.1% (50 of 1,231) of infants exposed to methimazole alone in the first trimester versus 2.1% (40 of 1,906) of no-medication controls; seven of the 1,231 methimazole-exposed infants had aplasia cutis congenita [3]. Aplasia cutis is a congenital skin defect in the infant, not an acquired hair or skin reaction in the mother [1][3].

The 2018 European Thyroid Association guideline says women treated with methimazole should be switched to propylthiouracil when planning pregnancy and during the first trimester [4].

Is pretibial myxedema a methimazole reaction?

Pretibial myxedema, or thyroid dermopathy, is an autoimmune manifestation of Graves' disease [5]. It is associated with high serum TSH-receptor antibody concentrations and often with ophthalmopathy [5]. In mild cases that do not require treatment, 50% of patients achieve complete remission after several years [5]. The methimazole label's minor skin entries are rash, urticaria, pruritus and skin pigmentation [1].

Frequently asked questions

›Does methimazole cause hair loss?

The label lists 'abnormal loss of hair' among minor adverse reactions, alongside skin rash, hives and itching [1]. It gives no incidence figure, type of alopecia, or typical onset or recovery time [1].

›What skin reactions does the label list?

The minor adverse reaction list includes skin rash, urticaria, pruritus and skin pigmentation [1]. The warning section separately describes vasculitis, including leukocytoclastic cutaneous vasculitis, which can occur with severe organ complications [1].

›What is the vasculitis warning?

The label warns that vasculitis with severe complications has been reported, most often ANCA-positive, and can include leukocytoclastic cutaneous vasculitis, kidney injury, pulmonary hemorrhage, CNS vasculitis and neuropathy [1]. If vasculitis is suspected, the label directs discontinuation of therapy and appropriate intervention [1].

›Is aplasia cutis a skin reaction in the mother?

No. Aplasia cutis congenita is a congenital skin defect reported in infants exposed to methimazole in the first trimester, among other rare congenital defects [1]. A study of 1,231 methimazole-exposed infants found seven cases [3].

›Does methimazole cause pretibial myxedema?

Pretibial myxedema is an autoimmune manifestation of Graves' disease, associated with high TSH-receptor antibody concentrations and often with ophthalmopathy [5]. The methimazole label lists rash, urticaria, pruritus and skin pigmentation as minor skin reactions [1].

›What should patients report?

The label says to report fever or sore throat immediately for possible agranulocytosis, and it names rash among the signs to report for possible vasculitis [1].

References

1. U.S. National Library of Medicine, DailyMed. Methimazole tablets USP (Chartwell RX) prescribing information. Methimazole tablets USP (Chartwell RX) label
2. Drugs@FDA: FDA-Approved Drugs. Drugs@FDA: FDA-Approved Drugs
3. Yoshihara A, Noh J, Yamaguchi T, Ohye H, Sato S, Sekiya K, et al. Treatment of graves' disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation. J Clin Endocrinol Metab. 2012;97(7):2396-403. Treatment of graves' disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation
4. Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism. Eur Thyroid J. 2018;7(4):167-186. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism
5. Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol. 2005;6(5):295-309. Pretibial myxedema: pathophysiology and treatment options