Volume: 05

Drug Information Centre (DIC) Indian Pharmaceutical Association, Bengal Branch Tele fax: 033 24612776, E-mail: ipabengal.dic@gmail.com Web Site: http://www.ipabengal.org Contact: 09830136291

Drug Information Bulletin (Electronic)

th

Year

Number: 30

6th November 2011

New Drug: Zonisamide CDSCO of India Letter F. No. 18-6/2011-DC: Limiting of Acetaminophen (paracetamol) in prescription combination products and giving box warning about Its Liver Toxicity- Recommendation of DTAB in Its 59th meeting held on 24.06.2011: Majority of Indians spend 70% of their income on medicines, healthcare: WHO FDA approves Bupivacaine Liposome Injectable Suspension India close to eliminating syphilis: NACO Forthcoming Event

Content

New Drug: Zonisamide (Available in different Brand name in Indian Market) Zonegran (Sci Gen) 25 mg, 50 mg and 100 mg capsules Approved indication: partial seizures Many adults with refractory epilepsy have partial seizures which may or may not become generalised. When monotherapy fails, it can be difficult to decide which adjunctive treatment will help the patient. Zonisamide adds to the list of drugs such as gabapentin, lamotrigine, tiagabine and topiramate, which can be used as add-on therapy. While it is a new drug in Australia, zonisamide has been available for many years in Japan. Zonisamide is a sulfonamide, but its mechanism of action in epilepsy is uncertain. It may stabilise neuronal membranes by blocking sodium and

calcium channels. Zonisamide is also a weak inhibitor of carbonic anhydrase. The capsules are well absorbed and food does not affect bioavailability. Zonisamide has a long half-life so it takes up to 14 days for its concentration to reach a steady state. The dose should therefore not be increased at intervals of less than one week. Treatment begins with twice-daily doses, but patients can switch to once daily after the dose has been titrated to an effective level. Most of the dose is excreted in the urine as unchanged drug and metabolites, so clearance falls with declining renal function. Doses may therefore need to be titrated more slowly in patients with renal or hepatic impairment. The metabolism of zonisamide includes cytochrome P450 3A4 so there is a potential for interactions with other drugs acting on this enzyme system. Clearance is increased by phenytoin,

2 sodium valproate and carbamazepine. Zonisamide may possibly interact with carbonic anhydrase inhibitors such as topiramate. A study in the USA compared zonisamide with placebo in 203 patients with refractory partial seizures. Different regimens were used to titrate the dose, but all patients randomised to take zonisamide were on 400 mg daily from the eighth week of the study. Patients continued their usual antiepileptic drugs. In the month before randomisation the median frequency of partial seizures was 13 in the placebo group and 1113 in the zonisamide groups. During weeks 812 of the study, the median frequency of all seizures was reduced by 9% in the placebo group and by 40.5% in the zonisamide group.1 Another American study randomised 152 patients to add zonisamide or a placebo to their usual treatment for 12 weeks. The dose of zonisamide was titrated over four weeks to 400600 mg daily. The baseline median frequency of seizures was approximately nine per month, but there was a 25.5% reduction after patients took zonisamide. In the placebo group there was a 6.6% increase in seizure frequency.2 In a European study 347 patients added a placebo or one of three doses of zonisamide to their usual therapy. The fixed-dose phase of the trial lasted for 18 weeks. During this phase, seizure frequency reduced by 17.4% in the placebo group and by 38.5% in patients taking zonisamide 300 mg daily. The efficacy of zonisamide 100 mg was not statistically different from placebo. While the median reduction in seizure frequency with zonisamide 500 mg was 46.1%, the response probably does not greatly increase above a daily dose of 400 mg.3 Frequent adverse effects with zonisamide include somnolence, dizziness and anorexia. Some patients lost weight during the trials.1,3 Adverse neurological events include ataxia, nystagmus, agitation and altered cognitive function. Driving skills may be impaired. Zonisamide can cause rashes, including Stevens-Johnson syndrome. The product information states that it is contraindicated if the patient has an allergy to sulfonamides. Prescribers may need to consider monitoring renal function as zonisamide has been associated with increases in urea and creatinine concentrations. Patients should be advised to maintain their hydration in warmer weather as oligohydrosis and hyperthermia have been reported (mainly in children). Early development of the drug in the USA was halted because 3.5% of patients developed kidney stones.1 Zonisamide is teratogenic in animals and is not approved for use in children. Although zonisamide reduces seizure frequency more than placebo, few patients will become free of seizures. Depending on the dose, a greater than 50% reduction in the frequency of all seizures is achieved by 3053% of patients. References* 1. Faught E, Ayala R, Montouris GG, Leppik IE; Zonisamide 922 Trial Group. Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures. Neurology 2001; 57:1774-9 . 2. Sackellares JC, Ramsay RE, Wilder BJ, Browne TR, Shellenberger MK. Randomized, controlled clinical trial of zonisamide as adjunctive treatment for refractory partial seizures. Epilepsia 2004; 45:610-17. 3. Brodie MJ, Duncan R, Vespignani H, Solyom A, Bitenskyy V, Lucas C. Dose-dependent safety and efficacy of zonisamide: a randomized, double-blind, placebo-controlled study in patients with refractory partial seizures. Epilepsia 2005; 46:31-41.

3 Source: (Aust Prescr 2011; 34:55-9) be added to the label of all prescription drugs products that contain Acetaminophen. USFDA has taken this action to make prescription combination pain medications containing Acetaminophen safer for patients use. Majority of Indians spend 70% of their income on medicines, healthcare: WHO Rising cost of diagnosis, medicines and hospitalisation will push millions of Indians below the poverty line, an official of the World Health Organisation (WHO) said on Tuesday. According to WHO regional advisor Dr Kathleen A Holloway, a majority of Indians spend around 70 per cent of their income on medicines and healthcare, compared to 30-40 per cent in other Asian countries like Sri Lanka. The problem is that they still suffer from the infected diseases in the absence of best quality of drugs and healthcare facilities. Due to out-of-pocket spending of their income in medicines and healthcare services, about 3.2 per cent of Indias population will fall below the poverty line (BPL), Dr Kathleen A Holloway said at a conference organised by the Delhi Society for Promotion of Rational Use of Drugs (DSPRUD) and WHO here. According to a survey by the International Institute of Population Sciences (IIPS) and WHO in six states, more than 40 per cent of low-income families in India have to borrow money from outside the family to meet their healthcare costs. The study found that 16 per cent families had been pushed below the poverty line by this trend. While spending has been soaring, experts said the issue of poor quality healthcare remains neglected. MCI (Medical Council of India) has received many complaints on the sideeffects of drugs prescribed by doctors.

Mother Teresa Inaugurating 29th National Pharmacy Week at Kolkata1990 CDSCO of India Letter F. No. 186/2011-DC: Limiting of Acetaminophen (paracetamol) in prescription combination products and giving box warning about Its Liver Toxicity- Recommendation of DTAB in Its 59th meeting held on 24.06.2011 The proposal of limiting of Acetaminophen (paracetamol) in prescription combination products and giving Box Warning about its liver toxicity was considered by the Drug Technical Advisory Board (DTAB) in its 59th meeting held on 24-Jun-2011 at New Delhi under the Chairmanship of Directorate General of Health Services. The proposal was based on USFDA News Release dated 13-Jan-2011 (118464). It has directed the manufacturers of prescription combination products in USA containing Acetaminophen to limit the amount of Acetaminophen to no more than 325mg in each tablet or capsule. In addition to this, a box warning highlighting the potential for severe liver injury and a warning of potential for allergic reaction to

4 Since there is less awareness among rural community about the medical council, majority of complaints received are from cities only, said MCI secretary Dr Sangeeta Sharma. Public hospitals in the country have grievance redressal committees in place, but not many people know about approaching the MCI, Dr Sangeeta Sharma added. [Source: IANS] FDA approves Bupivacaine Liposome Injectable Suspension MedPage Today reports the FDA has approved Pacira Pharmaceuticals' "nonopioid analgesic bupivacaine liposome injectable suspension [Exparel] for use in postsurgical pain relief." The safety of the medication "was established through 21 clinical trials of more than 1,300 patients, including 10 in which the suspension was administered through local surgical-site injections, in amounts ranging from 66 mg to 532 mg." India close to eliminating syphilis: NACO India is close to eradicating syphilis, one of the most common sexually transmitted infections (STIs), the National AIDS Control Organisation (NACO) said on Wednesday. There has been a tremendous decline in syphilis cases from all across the country. The cases have come down to 0.8 per cent and we could soon be close to elimination, NACO joint secretary Aradhana Johri said at the inauguration of the 12th Annual Congress of the International Union against STIs here. This has been possible through the regional centres, district level work for the high risk groups, colour-coded kits where even a non-professional worker at the STI clinic can provide treatment, Aradhana Johri added. Transmitted through sexual or even direct contact with the person with open sores or syphilis rash in the genital region, syphilis earlier accounted for around 10 per cent of cases in high-risk groups such as transgenders and sex workers. [Source: IANS] Forthcoming Event:

50th National Pharmacy Week Celebration 20th 27th November 2011 by Indian Pharmaceutical Association Bengal Branch Inauguration 20th November, 2011 Venue Science City Mini Auditorium, Kolkata 21.11.2011: Calcutta Institute of Pharmaceutical Technology & Allied Health Sciences, Uluberia, Howrah. 22.11.2011: EIILM, Kolkata. 23.11.2011: Industrial Pharmacy Day. Venue: Rotary Sadan, Kolkata. Time: 5.30 pm. 25.11.2011: Hospital Pharmacy Day. Venue: R.G.Kar Medical College, Kolkata. 26.11.2011: Students Day. Venue: Jadavpur University. 27.11.2011: Celebration at Durgapur. Venue: Hotel Ispat. *** Tentative programme

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