METOPIRONE Capsules Ref.[8619] Active ingredients: Mepyrapone

In relation to use as a diagnostic aid: anticonvulsants (eg phenytoin, barbiturates), anti-depressants and neuroleptics (eg amitriptyline, chlorpromazine), hormones that affect the hypothalamo-pituitary axis and anti-thyroid agents may influence the results of the Metopirone test. If these drugs cannot be withdrawn, the necessity of carrying out the Metopirone test should be reviewed.

If adrenocortical or anterior pituitary function is more severely compromised than indicated by the results of the test, Metopirone may trigger transient adrenocortical insufficiency. This can be rapidly corrected by giving appropriate doses of corticosteroids.

Long-term treatment with Metopirone can cause hypertension as the result of excessive secretion of desoxycorticosterone.

The ability of the adrenal cortex to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test, as Metopirone may induce acute adrenal insufficiency in patients with reduced adrenal secretory capacity, as well as in patients with gross hypopituitarism.

Patients with liver cirrhosis often show a delayed response to Metopirone, due to liver damage delaying the metabolism of cortisol.

In cases of thyroid hypofunction, urinary steroid levels may rise very slowly, or not at all, in response to Metopirone.

Patients with ectopic Cushing’s syndrome are at risk from opportunistic infections such as Pneumocystis Jirovecii pneumonia (previously termed Pneumocystis carinii pneumonia) during Metopirone treatment. Appropriate prophylactic treatment may be considered in this population.

When Metopirone is used as ACTH suppression test a diminished response was observed during pregnancy.

Anticonvulsants (e.g. phenytoin, barbiturates), psychotropic drugs (e.g. amitriptyline, chlorpromazine, alprazolam), hormone preparations, corticosteroids, antithyroid agents and cyproheptadine may affect the results of the Metopirone test (see Section 4.4, Special warnings and precautions for use).

Metopirone may potentiate paracetamol (acetaminophen) toxicity in humans.

Pregnancy

Unless the potential benefit outweighs the risk to the foetus Metopirone should not be given to pregnant women, since the drug can impair the biosynthesis of foetalplacental steroids. Animal reproduction studies adequate to evaluate teratogenicity and postnatal development have not been conducted with Metopirone (see section 5.3 Preclinical safety data).

Lactation

Since it is not known whether metyrapone passes into the breast milk, Metopirone should not be given to breast-feeding women.

Fertility

No data are available from animal reproduction studies.

Patients should be warned of the potential hazards of driving or operating machinery if they experience side effects such as dizziness and sedation.

Adverse drug reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000) very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.

Table 1. Adverse drug reactions:

Blood and the lymphatic system disorders

Not known: Bone marrow failure

Endocrine disorders

Rare: Adrenal insufficiency, Hypoadrenalism

Nervous system disorders

Common: Dizziness, sedation, headache

Vascular disorders

Common: Hypotension

Not known: Hypertension

Gastrointestinal disorders

Common: Nausea, vomiting

Rare: Abdominal pain

Skin and subcutaneous tissue disorders

Rare: Hirsutism, Allergic dermatitis

Not known: Alopecia

None stated.