Senpras 100, 300 & 400 100 mg, 300 mg, 400 mg Capsule

SENPRAS is indicated in controlling both simple and complex partial seizures with or without secondary generalised tonic clonic seizures in adults and children over 12 years of age. It is also used as adjunctive therapy in patients who have not achieved adequate seizure control with antiepileptic medicines, when used alone or in combination.

Posology
For all indications, a titration scheme for the initiation of therapy is described in Table 1, which is recommended for adults and children over the age of 12 years.

TABLE 1
DOSING CHART u2013 INITIAL TITRATION
Day 1 Day 2 Day 3
300 mg once a day 300 mg twice a day 300 mg three times a day

Epilepsy
Adults and children over 12 years: Usual effective dose: 900 u2013 1800 mg/day in three divides doses with not more than 12 hours between doses. Therapy should be initiated by titrating the dose as described in Table 1 above. Thereafter, the dose maybe increased to a maximum dose of 1 800 mg/day in three equally divided doses.

Elderly (over 65 years of age)
Elderly patients may require dosage adjustment because of declining renal function with age (see Table 2). Elderly patients should be closely monitored for adverse events.

Special populations
Renal impairment
Dosage adjustment is recommended in patients with compromised renal function as described in Table 2 and/or those undergoing haemodialysis.

TABLE 2
DOSAGE OF GABAPENTIN IN ADULTS BASED ON RENAL FUNCTION
Creatinine clearance (ml/min) Dose (mg/day) Dosing Regimen
> 60 1 200 400 three times a day
> 30 - 60 600 300 twice a day
15 - 30 300 300 once a day
< 15 150 300 every other day
Haemodialysis a - 200 - 300 b
a Loading dose of 300 to 400 mg
b Maintenance dose of 200 to 300 mg gabapentin following each 4 hours of haemodialysis

Discontinuation or dose reduction of gabapentin
In accordance with current clinical practice, if gabapentin requires a dose reduction, discontinuation or substitution of alternative anticonvulsant medication, it is recommended that this should be done gradually over a minimum of one week.

Paediatric population
The safety and efficacy of SENPRAS in children under the age of 12 years has not been established.

Method of administration
SENPRAS may be given orally with or without food and should be swallowed whole with sufficient fluid intake (e.g. a glass of water).

• SENPRAS is contraindicated in patients with hypersensitivity to gabapentin or to any of the excipients (see section 6.1).
• The safety and efficacy in children under the age of 12 years has not been established.
• The safety and efficacy in pregnancy or breastfeeding has not been established (see section 4.6).
• Severe renal impairment.

Drug rash with Eosinophilia and Systemic symptoms
Drug rash with eosinophilia and systemic symptoms (DRESS) has been reported in patients taking antiepileptic medicines including gabapentin (see section 4.8). Some of these reactions are severe and life-threatening. DRESS typically presents with manifestations of hypersensitivity, such as fever or lymphadenopathy, even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. SENPRAS should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

Anaphylaxis
Gabapentin can cause anaphylaxis. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue SENPRAS and seek immediate medical care should they experience signs or symptoms of anaphylaxis (see section 4.8).

Suicidal ideation and behaviour
Antiepileptic medicines, including gabapentin, increase the risk of suicidal thoughts or behaviour in patients taking these medications. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Acute pancreatitis
Discontinuation of SENPRAS should be considered if a patient develops acute pancreatitis while on treatment with SENPRAS, (see section 4.8).

Seizures
Although there is no evidence of rebound seizures with gabapentin, antiepileptic medicines should not be abruptly discontinued because of the possibility of increasing seizure frequency.

Somnolence/Sedation and Dizziness
Gabapentin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall). Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.

Concomitant use with opioids
Patients who require concomitant treatment with opioids such as morphine, should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression. The dose of SENPRAS or opioids should be reduced appropriately (see section 4.5).

Respiratory depression
Gabapentin has been associated with severe respiratory depression. Patients who have a higher risk of experiencing severe respiratory depression are those that have compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and the elderly. Dose adjustments might be necessary in these patients.

Elderly (over 65 years of age)
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.

Paediatric population
Safety and effectiveness in children under 12 years has not been established.

Abuse and dependence
Cases of abuse and dependence have been reported. Careful evaluation of patients with a history of drug abuse should be observed for possible signs of gabapentin abuse e.g. drug-seeking behaviour, dose escalation, development of tolerance.

Laboratory tests
Because false positive readings were reported with the Ames N-Multistix SG u00ae dipstick test for urinary protein when gabapentin was added to other antiepileptic medicines, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein.

Gabapentin is not appreciably metabolised, nor does it interfere with the metabolism of commonly co-administered antiepileptic medicines such as phenytoin, carbamazepine, valproic acid and phenobarbitone.

Morphine
When SENPRAS is administered with morphine, patients should be observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression.

Oral contraceptives
Concurrent use of SENPRAS with oral contraceptives containing norethindrone and/or ethinyl estradiol does not influence the steady-state pharmacokinetics of either component.

Antacids
Antacids containing magnesium and aluminium hydroxides reduced the mean bioavailability of gabapentin by about 20 %. It is recommended that SENPRAS be taken about two hours before or after antacid administration.

Probenecid
Renal excretion of gabapentin is unaltered by probenecid.

Cimetidine
A slight decrease in renal excretion of SENPRAS by cimetidine is observed and is not expected to be of clinical importance.

Laboratory tests
Because false positive readings were reported with the Ames N-Multistix SG u00ae dipstick test for urinary protein when gabapentin was added to other antiepileptic medicines, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein.

Pregnancy
SENPRAS should not be used during pregnancy as safety and efficacy has not been established. Animal studies have shown reproductive toxicity. The potential risk in humans is not known.

Breastfeeding
SENPRAS is excreted in human milk. The effect on the breastfed infant and on milk production is not known, therefore SENPRAS should not be used in breastfeeding mothers.

Fertility
There is no effect on fertility in animal studies.

Gabapentin causes somnolence, drowsiness and dizziness. Patients taking SENPRAS should not drive or operate complex machinery until they have gained sufficient experience to assess whether SENPRAS impairs their ability to drive or operate such machinery.

a. Summary of the safety profile
MedDRA system organ class Frequency Adverse reactions
Infections and infestations Frequent Viral infection, respiratory infection, pneumonia, urinary tract infection, otitis media
Blood and lymphatic system disorders Frequent Leukopenia
Immune system disorders Less frequent Allergic reactions
Metabolism and nutrition disorders Frequent Anorexia, increased appetite
Less frequent Hyperglycaemia or hypoglycaemia (most often seen in diabetic patients)
Psychiatric disorders Frequent Confusion, depression, emotional lability, nervousness, thinking abnormal, hostility, anxiety
Less frequent Agitation
Nervous system disorders Frequent Ataxia, dizziness, somnolence, amnesia, abnormal coordination, dysarthria, insomnia, headache, nystagmus, tremor
Less frequent Hypokinesia, mental impairment, loss of consciousness
Eye disorders Frequent Visual disturbances such as amblyopia, diplopia
Ear and labyrinth disorders Frequent Vertigo
Cardiac disorders Less frequent Palpitations
Vascular disorders Frequent Vasodilation, hypertension
Respiratory, thoracic and mediastinal disorders Frequent Coughing, pharyngitis, rhinitis, bronchitis, dyspnoea
Less frequent Respiratory depression
Gastrointestinal disorders Frequent Abdominal pain, constipation, dental abnormalities, diarrhoea, dyspepsia, dry mouth or throat, nausea and/or vomiting, gingivitis, flatulence
Less frequent Dysphagia
Skin and subcutaneous tissue disorders Frequent Acne, pruritus, rash, facial oedema, purpura
Musculoskeletal and connective tissue disorders Frequent Back pain, myalgia, twitching, arthralgia
Reproductive system and breast disorders Frequent Impotence
General disorders and administration site conditions Frequent Fatigue, Fever, peripheral oedema, abnormal gait, pain, malaise, flu syndrome
Less frequent Generalised oedema
Investigations Frequent WBC (white blood cell count) decreased, weight increase
Less frequent Elevated liver function tests and bilirubin
Injury, poisoning and procedural complications Frequent Abrasion, fracture
Less frequent Fall
Postmarking experience
The following additional adverse reactions have been reported:
MedDRA system organ class Adverse reactions
Blood and lymphatic system disorders Thrombocytopenia
Immune system disorders Hypersensitivity syndrome (systemic reaction that can include fever, rash, hepatitis, lymphadenopathy, eosinophilia, anaphylaxis
Metabolism and nutrition disorders Hyponatraemia
Psychiatric disorders Hallucinations
Nervous system disorders Other movement disorders (e.g. dyskinesia, dystonia, choreoathetosis)
Ear and labyrinth disorders Tinnitus
Gastrointestinal disorders Pancreatitis
Hepatobiliary disorders Hepatitis, jaundice
Skin and subcutaneous tissue disorders Steven-Johnsons syndrome, angioedema, erythema multiforme, alopecia, rash with eosinophilia and systemic symptoms
Musculoskeletal and connective tissue disorders Myoclonus, rhabdomyolysis
Renal and urinary disorder Acute renal failure, incontinence
Reproductive system and breast disorders Breast hypertrophy, gynaecomastia, sexual dysfunction (changes in libido, ejaculation disorders, anorgasmia)
General disorders and administration site disorders Withdrawal reactions (anxiety, nausea, pains, insomnia, sweating), chest pain
Investigations Blood creatinine phosphokinase increased
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Acute oral overdoses of gabapentin up to 49 grams have been reported. In these cases, double vision, slurred speech, drowsiness, lethargy, loss of consciousness and diarrhoea were observed. All patients recovered with supportive care. Overdoses of gabapentin, in particularly with CNS depressant medicines, may result in coma. Gabapentin can be removed by haemodialysis. Although haemodialysis is usually not required, it may be indicated by the patientu2019s clinical state or in patients with significant renal impairment. Treatment is symptomatic and supportive.