Kynmobi® (apomorphine hydrochloride) sublingual film

Prescribing Information

Kynmobi® (apomorphine hydrochloride) sublingual film.

Please refer to the SPC for full information before prescribing.
Presentation: Sublingual film containing 10 mg, 15 mg, 20 mg, 25 mg or 30 mg apomorphine hydrochloride. Packs of 15 and 30 films. Treatment initiation pack containing 10 sublingual films, 2 of 10 mg, 15 mg, 20 mg, 25 mg, 30 mg each.
Indication: Kynmobi is indicated for the intermittent treatment of “OFF” episodes in adult patients with Parkinson’s disease (PD) which are not sufficiently controlled by oral anti-Parkinson medication.
Posology and method of administration: Patients selected for treatment with Kynmobi should be able to recognise the onset of their “OFF” symptoms. If domperidone (an antiemetic) is considered medically warranted, then the lowest effective domperidone dose should be utilized and discontinued as soon as possible. Before the decision to initiate domperidone and apomorphine treatment, risk factors for QT interval prolongation in the individual patient should be assessed. Kynmobi should be initiated in the controlled environment of a specialist clinic. The patient should be supervised by a trained healthcare professional experienced in the treatment of PD (e.g. Neurologist). Titration: The appropriate dose for each patient is established by incremental dosing schedules. The following schedule is recommended: The initial dose of Kynmobi is 10 mg. Dose initiation should occur when the patient is having an “OFF” episode. If the patient tolerates the 10 mg dose, and responds adequately (satisfactory motor response within 30 minutes), the maintenance dose should be 10 mg. If the dose is tolerated but the response is insufficient, continue to titrate in 5 mg increments when the patient is having an “OFF” episode and assess response until an effective and tolerable dose is achieved, up to a maximum of 30 mg per dose, up to five times a day. The minimal interval between doses is 2 hours, with no more than one dose of Kynmobi for an “OFF” episode. Kynmobi is available as a treatment initiation pack, containing two sublingual films of each strength. Maintenance: Once the appropriate dose is determined Kynmobi may be taken, as needed, up to 30 mg up to five times a day. The minimal interval between doses is 2 hours. The total maximum daily dose is 150 mg. Once established, the optimal dose of Kynmobi, remains relatively constant for each patient. Elderly: The management of elderly patients treated with Kynmobi has not differed from that of younger patients. There is a higher risk of postural hypotension in elderly patients, therefore particular caution should be exercised during the initiation of treatment. Renal impairment: No dose adjustment is required for patients with mild or moderate renal impairment. No clinical experience in patients with severe renal impairment. The use of Kynmobi is not recommended in patients with severe and end-stage renal disease (ESRD) (CrCl <30 mL/min). Hepatic impairment: Not recommended. Method of administration: For sublingual use. The sublingual film should dissolve under the tongue. It must be administered whole, must not be cut, chewed, or swallowed.
Contraindications: Hypersensitivity to the active substance or to any of the excipients. Co-administration with 5HT3 antagonists (e.g. ondansetron, granisetron, dolasetron, palonosetron and alosetron). Concomitant use with ondansetron. Dementia. Psychotic disorder. Cankers or mouth sores. Hepatic impairment. Respiratory depression.
Special warnings and precautions for use: Kynmobi should be given with caution to patients with pulmonary or cardiovascular disease and persons prone to nausea and vomiting. Syncope, hypotension or orthostatic hypotension: Kynmobi may cause syncope, hypotension or orthostatic hypotension. Patients should be instructed to rise slowly after sitting or lying down after taking Kynmobi. Care should be exercised in patients with pre-existing postural hypotension. The hypotensive effects of Kynmobi may be increased by the concomitant use of antihypertensive medications, vasodilators (especially nitrates) and alcohol. Cardiac symptoms and other related disorders: The patient should be instructed to report possible cardiac symptoms including palpitations, syncope, or near-syncope. They should also report clinical changes that could lead to hypokalaemia, such as gastroenteritis or the initiation of diuretic therapy. QTc prolongation and potential for proarrhythmic effects: Since apomorphine, especially high doses, may have the potential for QT prolongation, caution should be exercised when treating patients at risk for torsades de pointes arrhythmia. The risks and benefits of Kynmobi should be considered prior to treatment with Kynmobi in patients with risk factors for prolonged QTc. Oropharyngeal adverse events: Kynmobi may cause oral mucosal irritation, including erythema in the oral cavity (tongue, lips, gingiva), oral soft tissue swelling (lips, tongue, gingiva), and infrequently systemic hypersensitivity, including facial flushing, increased lacrimation, swelling of the face, or urticaria. It is not known whether these events are related to apomorphine, or any other excipient. Kynmobi rechallenge is not recommended after discontinuation as oral adverse reactions may recur and be more severe than the initial reaction. Neuropsychiatric disorders: For some patients, neuropsychiatric disturbances may be exacerbated by apomorphine. Special care should be exercised when apomorphine is used in these patients. Kynmobi should not be considered for patients with a major psychotic disorder unless the potential benefits outweigh the risks and uncertainties. Sudden onset of sleep and somnolence: Apomorphine has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Patients must be informed of this and advised to exercise caution whilst driving or operating machines. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Reduction of dose may be considered. Impulse Control Disorders: Patients should be regularly monitored for the development of ICDs. Patients and carers should be made aware that behavioural symptoms of impulse control disorders can occur. Dose reduction/tapered discontinuation should be considered if such symptoms develop. Dopamine dysregulation Syndrome (DDS): This is an addictive disorder resulting in excessive use of the medicinal product seen in some patients treated with apomorphine. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing DDS. Dopamine Agonist Withdrawal Syndrome (DAWS) A drug withdrawal syndrome has been reported during tapering or after discontinuation of dopamine agonists. Withdrawal symptoms do not respond to levodopa, and may include apathy, anxiety, depression, fatigue, sweating, panic attacks, insomnia, irritability, and pain. The syndrome has been reported in patients who did or did not develop impulse control disorders. Prior to discontinuation, patients should be informed about potential withdrawal symptoms, and closely monitored during tapering and after discontinuation. Neuroleptic malignant syndrome: A symptom complex resembling neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, elevated serum creatine kinase, and autonomic instability) with no other obvious aetiology has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy. Haemolytic anaemia and thrombocytopenia: Haemolytic anaemia and thrombocytopenia have been reported in patients treated with apomorphine. Haematology tests should be undertaken at regular intervals as with levodopa, when given concomitantly with apomorphine. Others: Apomorphine use is associated with increased incidences of penile erection. They may develop into prolonged painful erections requiring medical attention. Excipients: Kynmobi contains sodium metabisulphite, which may rarely cause severe allergic reactions and bronchospasm. This medicinal product contains less than 1 mmol sodium (23 mg) per film, i.e. essentially “sodiumfree”.
Interaction with other medicinal products and other forms of interaction: In the initial stages of therapy, the patient should be monitored for unusual side-effects or signs of potentiation of effect. Concomitant use of 5HT3 antagonists, including antiemetics, is contraindicated. Concomitant use of apomorphine with ondansetron may lead to severe hypotension and loss of consciousness and is therefore contraindicated. Please consult the SPC before prescribing Kynmobi to patients receiving neuroleptic medicinal products (e.g. clozapine), domperidone, alcohol, antihypertensive medications, vasodilators. Caution is advised when combining apomorphine with other medicinal products, especially those with a narrow therapeutic range.
Fertility, pregnancy and lactation: Pregnancy: Not recommended during pregnancy and in women of childbearing potential not using contraception. Breast- feeding: It is unknown whether apomorphine /metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded.
Effects on ability to drive and use machines: Kynmobi has moderate influence on the ability to drive and use machines. Apomorphine may cause dizziness, symptomatic orthostatism, and somnolence. Therefore, caution should be exercised when driving or using machines.
Undesirable effects: Summary of the safety profile: The most common adverse reactions reported in pooled analyses for two phase II and two phase III clinical studies were nausea (20.5%) during titration phase, and nausea (22.0%), somnolence (8.5%) and dizziness (5.9%) during maintenance phase. Oropharyngeal adverse events (swelling, oedema, pain, irritation, ulceration) were also commonly observed in the patients treated with Kynmobi. List of adverse reactions: Very common (≥ 1/10): Somnolence, Yawning, Nausea Oral soft tissue sign and symptoms*; Stomatitis and ulceration; Tongue conditions; Common (≥ 1/100 to < 1/10): Oral candidiasis; Hallucination; Dizziness; Dyskinesia; Headache; Syncope; Transient sedation; Vision blurred; Orthostatic hypotension; Hypotension; Hot flush; Hypertension; Flushing; Rhinorrhoea; Dyspnoea; Vomiting; Oral soft tissue swelling and oedema; Oral dryness and saliva altered; Oral soft tissue disorder; Retching; Gingival disorder, signs and symptoms; Rash; Hyperhidrosis, Cold sweat; Fatigue; Feeling abnormal; Feeling cold; Chills; Fall; Oropharyngeal Adverse Events: As Kynmobi is administered sublingually, irritation, erythema, oedema, ulceration, pain, para/dysesthesias of oral cavity, teeth colour change, caries, changes in salivary gland secretion were observed in clinical studies. Oral soft tissue sign and symptoms commonly observed in patients treated with Kynmobi, included oral mucosal erythema, hypoaesthesia oral, oral discomfort, oral mucosal blistering. For most subjects, events were tolerated or resolved either spontaneously or soon after discontinuation of treatment. Kynmobi rechallenge is not recommended after discontinuation as oral adverse reactions may recur and be more severe than the initial reaction. Transient sedation: Transient sedation with each dose of apomorphine hydrochloride at the start of therapy may occur; this usually resolves over the first few weeks.
Overdose: There is little clinical experience of overdose with apomorphine by the sublingual route of administration. Symptoms of overdose may be treated empirically as suggested in the following: excessive emesis may be treated with domperidone; respiratory depression may be treated with naloxone; hypotension: appropriate measures should be taken, e.g. raising the foot of the bed; bradycardia may be treated with atropine.
Special precautions for storage: Do not store above 25 °C. Store in the sachet to protect from light and moisture.
Legal Category: POM.
Basic UK NHS cost: Kynmobi Titration Pack x 10 films £48.10, Kynmobi 10 mg sublingual film x 30 £144.30, Kynmobi 15 mg sublingual film x 30 £144.30, Kynmobi 20 mg sublingual film x 30 £144.30, Kynmobi 25 mg sublingual film x 30 £144.30, Kynmobi 30 mg sublingual film x 30 £144.30,
Marketing Authorisation Holder: Bial - Portela & Cª, S.A., À Av. da Siderurgia Nacional 4745-457 S. Mamede do Coronado, Portugal.
Marketing Authorisation number(s):; PL 21566/0010, PL 21566/0011, PL 21566/0012, PL 21566/0013, PL 21566/0014, PL 21566/0015

Date of preparation: May 2024. Job code: UK/KM/2024/001