March 2019 new listings wrap-up

Insulin lispro (Humalog) has been listed on the PBS General Schedule (Section 85) at a higher strength (200 units/mL).^1,2

What is it?

Insulin lispro (Humalog U200) is an aqueous solution of human insulin analogue with a rapid onset of action and short duration of activity.³

It is administered subcutaneously at 200 units/mL in a 3 mL prefilled delivery device (KwikPen).³

Who is it for?

Insulin lispro (Humalog U200 KwikPen) is indicated for the treatment of patients with type 1 and type 2 diabetes who require insulin for the maintenance of normal glucose homeostasis.³

It may meet a clinical need for patients who require high daily doses of insulin lispro.⁴

Safety issues

Insulin lispro 100 units/mL is also administered using the KwikPen device.² Advise patients to take care that they use the correct cartridge (200 units/mL).

Insulin lispro 200 units/mL should not be transferred from the prefilled KwikPen device to a syringe (or any other insulin delivery device), as markings on the syringe will not measure the dose correctly.³

Insulin lispro is contraindicated in patients with hypoglycaemia.³

Ixekizumab (Taltz) has been listed on the PBS General Schedule for patients with severe active psoriatic arthritis.¹

What is it?

Ixekizumab is a recombinant humanised monoclonal antibody that inhibits the activity of interleukin-17A, a cytokine involved in inflammatory and immune responses.⁵

Who is it for?¹

Ixekizumab is now PBS-listed for patients aged 18 years and over who are treated by a rheumatologist or clinical immunologist with expertise in the management of psoriatic arthritis.

At any one time, a person may not also receive PBS-subsidised treatment with adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, secukinumab or ustekinumab.

Treatment and clinical criteria are specific to treatment cycle and phase (initial, continuing or grandfathered treatment).

In general, a patient may receive long-term treatment with a biological medicine within a single treatment cycle as long as they sustain a treatment response.

They cannot trial and fail to respond, or stop responding to the same PBS-subsidised biological medicine more than once in a treatment cycle.

Patients require a minimum 5-year break from treatment with a PBS-subsidised biological medicine if they do not respond or stop responding to biological medicine three times.

If a patient has been treated unsuccessfully with fewer than three medicines in a treatment cycle and has a treatment break for more than 5 years, they may commence a new treatment cycle. If the treatment break is less than 5 years, they may commence a further course of treatment within the same treatment cycle.

There is no limit to the number of treatment cycles a patient may undertake in their lifetime.

Safety issues⁵

Immunosuppression may increase the risk and severity of infection. Ixekizumab should not be used if a patient has a serious or untreated infection, such as sepsis, hepatitis B or active tuberculosis (TB).

Ixekizumab can potentially reactivate latent TB, so TB treatment should be started before starting ixekizumab.

Consider the need for immunisation before starting ixekizumab. Live vaccines should not be used during treatment.

Lenvatinib (Lenvima) has been listed on the PBS General Schedule for patients with advanced hepatocellular carcinoma.¹

What is it?

Lenvatinib inhibits specific kinases that are abnormally activated in some cancers.⁶

These kinases include the vascular endothelial growth factor (VEGF) receptor types 1–3, fibroblast growth factor receptor types 1–4, platelet-derived growth factor receptor, c-Kit and RET.⁶

Who is it for?¹

Lenvatinib is now PBS-listed for patients with advanced (unresectable) Barcelona Clinical Liver Cancer Stage B or Stage C hepatocellular carcinoma.

To receive initial treatment with lenvatinib, patients must not be suitable for transarterial chemoembolisation, and they must have a WHO performance status of 2 or less and Child-Pugh A liver disease.

In addition, they must have not received prior treatment with a VEGF tyrosine kinase inhibitor (TKI) for this condition or must have developed intolerance to a VEGF TKI leading to permanent treatment withdrawal.

Lenvatinib could provide patients with an alternative to sorafenib for treatment of hepatocellular carcinoma.⁷

Safety issues⁶

Lenvatinib can cause hypertension, prolong the QT interval and increase risk of arrythmia.

Hypertension should be controlled before starting lenvatinib, risk factors should be corrected, and blood pressure should be monitored during treatment.

For more information see the Australian Prescriber article Risk assessment of drug-induced QT prolongation.

Serious tumour-related bleeds have been reported following treatment with lenvatinib. Consider a patient’s bleeding risk and use with caution.

Diarrhoea and nausea are common adverse events with lenvatinib treatment. A management plan for vomiting and diarrhoea is recommended for patients prescribed lenvatinib.

Tiotropium bromide (Spiriva Respimat) has been listed on the PBS General Schedule for the treatment of paediatric patients with severe asthma.¹

What is it?

Tiotropium bromide is a long-acting muscarinic antagonist (LAMA) with similar affinity for muscarinic receptor subtypes M₁ to M₅.⁸

Inhibition of muscarinic M_3¬ receptors in the airways leads to smooth muscle relaxation and bronchodilation.^8,9

Who is it for?¹

Tiotropium bromide (Spiriva Respimat) is now PBS-listed for patients aged 6–17 years (inclusive) with severe asthma.

Patients must be treated by (or in consultation with) a respiratory physician, paediatric respiratory physician, clinical immunologist, allergist, paediatrician or general physician experienced in the management of severe asthma.

They must have failed to achieve adequate control with optimised asthma therapy, despite formal assessment of, and adherence to, correct inhaler technique.

To receive PBS-subsidised treatment, tiotropium must be used in combination with an inhaled corticosteroid and a long-acting beta-2 agonist (unless contraindicated).

In addition, patients must have had at least one severe exacerbation that required documented use of systemic corticosteroids in the previous 12 months while receiving optimised asthma therapy.

Alternatively, they must have had frequent episodes of moderate asthma exacerbations.

Safety issues⁹

Tiotropium is also administered using the HandiHaler device (for chronic obstructive pulmonary disease). Advise patients to take care that they follow instructions for asthma treatment using Spiriva Respimat cartridges with the Respimat inhaler device.

Ensure the mist from the Respimat device does not come in contact with the eyes.

Dry mouth and throat irritation are common adverse events with anticholinergics.

Advise patients and educate parents of young children taking tiotropium to tell their doctor if they notice any eye pain or discomfort, disturbed vision or difficulty urinating.

Tiotropium is a LAMA, and is not for immediate relief of asthma symptoms.

Venetoclax (venclexta) has been listed on the PBS General Schedule for the treatment of chronic lymphocytic leukaemia (CLL).¹

What is it?

Venetoclax inhibits the B cell lymphoma 2 (BCL-2) protein, an anti-apoptotic protein overexpressed in CLL cells. Inhibition of the BCL-2 protein by venetoclax triggers cell death.¹⁰

Who is it for?

Venetoclax is PBS-listed for patients with CLL, although clinical criteria are specific to different treatment phases (initial dose titration or extension to dose titration, continuing treatment or grandfathered treatment).¹

For initial treatment (dose titration), patients:

• must be unsuitable for treatment or retreatment with a purine analogue,
• must have an ECOG/WHO performance status of 0 or 1, and
• their condition must have relapsed or be refractory to at least one prior therapy.

Venetoclax must be used as monotherapy under this restriction.

For continuing treatment, venetoclax must be used in combination with rituximab for a maximum of six cycles, then used as monotherapy.

In addition, venetoclax treatment must be stopped on disease progression or following 24 months of PBS-subsidised treatment, whichever comes first.

Safety issues

Venetoclax can cause rapid tumour reduction. There is a risk of tumour lysis syndrome (TLS) during the initial 5-week titration phase.¹¹

Electrolyte changes consistent with TLS can occur as early as 6 to 8 hours following the first dose and at each dose increase.¹¹

Tumour burden and blood chemistry assessments should be conducted prior to initiation of treatment.¹¹

TLS prophylaxis and monitoring measures are described in the venetoclax product information.¹¹

Venetoclax can cause neutropenia. Avoid combining with other neutropenic agents.^10,11

Venetoclax is metabolised by CYP3A4 and is a substrate of P-glycoprotein. Venetoclax concentration and risk of toxicity may increase if given with CYP3A4 or P-glycoprotein inhibitors.¹⁰

Concomitant use of venetoclax with strong CYP3A inhibitors at initiation and during dose titration is contraindicated.¹¹