Clinical Pharmacology

"Adverse Drug Event of the month"

Intracranial hemorrhage with an Ayurvedic preparation: Possible causal relationship

Alternative medicine or Complementary and alternative medicine (CAM) has gained increasing attention in recent years with regard to both cure and potential health hazards^[1]. 80 % of the world's population and 70-80 % of Indian population relies on these medicine since they are considered free from side effects^[2]. In addition patients may not necessarily inform their physician about their use.

We report a case of possible intra cranial hemorrhage following the administration of an Ayurvedic proprietary medicine and implication of the same. A 40 year old female patient presented to the casualty of Seth G.S. Medical college & KEM Hospital with slurring of speech, left sided deviation of mouth and weakness in right upper limb, which lasted for 2 hours. Her blood pressure was 160/110 mm of Hg.X-ray and E.C.G. findings were within normal limits. Biochemical investigations were also within normal limits. A CT scan revealed recent hemorrhage in left lentiform nucleus and internal capsule of hypertensive etiology with no evidence of brainstem herniation. The patient was diagnosed with right faciobrachial palsy. Her detailed history revealed she was nonhypertensive, nondiabetic, no history of head injury, history of tubal ligation 6 years back and not on any other medication except "Aloes compound". The patient was taking "Aloes compound" for Oligomenorrhoea prescribed by an Ayurvedic physician practising allopathy in the dose of 2 tablets twice a day since 45 days. These tablets were then stopped and intravenous mannitol and atenolol 25 mg. per day. was started for control of blood pressure, which normalized within 6 hours. She was kept under observation and discharged on day 5 and atenolol was slowly withdrawn over 2 weeks. At one month and three months follow up, her blood pressure was 120/80 mm of Hg.

An analysis by our Ayurvedic physicians revealed that the drug had been prescribed in the right dose but to the "wrong" patient. The patient had "Pitta Vata" "prakriti" or constitution. As per Ayurvedic principles, examination of a patient's constitution analysis precedes disease history and determines what drugs are to be prescribed. Aloes compound (batch no. 55201) which contains Aloe vera 70 mg., Commiphora myrrha (hirabol) 70 mg., Leptadenia reticulata (Jivanti) 30 mg., Rubia cordifolia (Manjishtha) 35 mg., Paganum harmala (Harmal) 35 mg., Kamboji 30 mg. and iron sulphate (Kasis bhasma) 30 mg. is contraindicated in patients with this constitution. ^[3], ^[4] The drug analysis report from forensic medicine concluded, there is no ingredient that could have anticoagulant activity, and lead to intra- cranial bleeding. As per Ayurvedic texts, cardiovascular adverse events such as syncope and palpitations have been attributed to Harmal^[5]. Studies on active alkaloids of hermala too states similar toxicity^[6] and Kasis bhasma which is an organometalic ash must be fully purified or else can cause severe adverse events^[7]. In view of lack of any other medication, the rise in blood pressure could be attributed to "Aloes compound" and this could have resulted from inadequate purification or incorrect prescribing. As per the Naranjo's algorithm for estimating Adverse Drug Reaction, the score is 4, which denotes the reaction as the "possible" reaction.^[8]

The causal effect relationship between the use of the Ayurvedic formulation and the symptoms, is strengthened by the absence of any other cause for the hemorrhage and normalization of blood pressure with drug dechallenge. Today, safety monitoring of non-allopathic medicines is the joint responsibility of the allopathic pharmacologists, physicians and practitioners of the respective systems of medicines. Detailed history taking is also an important aspect, and the patients also need to be educated on the risks that alternative medicines carry.

References:

1. Stickel F, Seitz HK. The efficacy and safety of comfrey. Pub health nutr 2000; 3: 501-508.

2. Ernst E. Harmless herbs? A review of the recent literature. Am J Med 1998; 104: 170-178.

3. Nayak B. Ayurmedline. Ayurmedline,Bangalore (India).Jan-June 2001.

4. Sharma RK, Dash B. Charaka samhita 6th ed. Varanasi (India): Chaukhamba sanskrit studies, 1999.

5.Gogate VM. The text book of Ayurvedic pharmacology and therapeutics of medicinal plants. Mumbai ( India ): Bhartiya vidya bhawan,2000.

6. Aarons DH, Rosi GV, Orzechowski RF.Cardiovascular actions of three harmala alkaloids: Harmine, harmaline and harmolol. J Pharm Sci 1977;66: 1243-1247.

7. Joshi D, Rao GP. Rasamritam.Varanasi (India) 1998.1st ed.Chaukhambha sanskrit Bhavan

8.Naranjo CA, Busto U et al.A method for estimating the probability of adverse drug reactions. Clin Pharmacol. Ther. 1981; 30: 239- 245.



Department of Clinical Pharmacology,
MS building, 1st floor,
Seth GS Medical College & KEM Hospital,
WHO Special Centre for Adverse Reactions Monitoring Parel,
Mumbai-400012.
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