ALKINDI

What it is

ALKINDI is hydrocortisone provided as granules in capsules. ALKINDI is available in strengths of 0.5 mg, 1 mg, 2 mg and 5 mg per capsule. The granules are white to off-white and contained in a transparent colourless hard capsule. ALKINDI was developed for use in patients requiring smaller doses.

Approved indications

— Replacement therapy of adrenal insufficiency.

Dosing overview

Recommended replacement doses of hydrocortisone are 8–10 mg/m²/day for patients with adrenal insufficiency alone and 10–15 mg/m²/day in patients with congenital adrenal hyperplasia (CAH), typically in three or four divided doses. Dose must be individualised according to the response of the individual patient, and the lowest possible dose should be used. Monitoring of clinical response is necessary and patients should be observed closely for signs that might require dose adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual responsiveness to the medicinal product, and the effect of stress such as surgery, infection and trauma. During stress it may be necessary to increase the dose temporarily.

Key safety warnings

Sudden discontinuation of therapy with hydrocortisone risks triggering an adrenal crisis and death. Where a child is vomiting or acutely unwell parenteral hydrocortisone should be started without delay, and carers should be trained in administering this in an emergency. Adrenal crisis can occur when switching from conventional oral hydrocortisone formulations (crushed, split or compounded) to ALKINDI, and close monitoring of patients is recommended in the first week after the switch. Corticosteroids may cause growth retardation in infancy, childhood and adolescence, which may be irreversible. Treatment should be limited to the minimum dose required to achieve desired clinical response and when reduction in dose is possible, the reduction should be gradual. Infants require frequent assessment and should be evaluated at a minimum every 3 to 4 months to assess growth, blood pressure and general well-being. Potentially severe psychiatric adverse reactions including euphoria, mania, psychosis with hallucinations and delirium have been seen in adult patients at replacement doses of hydrocortisone, with symptoms typically emerging within a few days or weeks of starting treatment. Patients and carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Visual disturbance may be reported with systemic corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy.

Contraindications

Hypersensitivity to the active substance or to any of the excipients. Patients with dysphagia or premature infants where oral feeding has not been established.

Regulatory history

ALKINDI received initial approval on 18 August 2020. The Pharmaceutical Benefits Advisory Committee recommended ALKINDI in July 2021 for adrenal insufficiency, and in September 2023 recommended an extension of the recommendation for an additional 6 months for use in adrenal insufficiency in children aged 6 or younger.