Download Fatality From Spasmo-Proxyvon® Addiction: A Few Cases

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Case Report
Fatality From Spasmo-Proxyvon® Addiction: A Few Cases
Venkata Raghava S,* Vijay Kautilya D, Bheemappa Havanur, Devadass PK
ABSTRACT
Ever since the information technology revolution hit India in a big way, substance abuse has been rising in incidence by leaps and bounds, mainly because of the ease
with which such substances can be procured through
the Internet. There has been a significant shift from conventional drugs of abuse such as cannabis and heroin to
newer drugs such as designer amphetamines, phencyclidine, and ketamine.
But because these drugs are covered by the Narcotic
Drugs and Psychotropic Substances Act, there has been
a recent trend towards abuse of pharmaceutical agents
such as pentazocine, propoxyphene and buprenorphine.
Spasmo-Proxyvon® is a popular brand of antispasmodic
from Wockhardt which contains paracetamol (acetaminophen), dicyclomine, and dextropropoxyphene. This
combined drug formulation sold as gelatin capsules is easily
available, and is increasingly being abused for its opioid
effect. A few cases of such addiction resulting in death
are being reported.
Case 1
A 31-year-old male developed rigor all on a sudden while
in his bathroom, which persisted for 10-15 minutes even
after coming out of the bathroom, and died thereafter.
Autopsy revealed bluish-coloured semi-digested rice particles in the stomach with unusual smell, and congestion
of the mucosa. Intestinal mucosa was also congested.
Blood and viscera samples were sent for chemical analysis to the Forensic Science Laboratory. Testing revealed
the presence of dextropropoxy-phene.
Key Words: Spasmo-Proxyvon®; Dextropropoxyphene;
Acetaminophen; Paracetamol; Dicyclomine
Case 2
A 20-year-old male developed sudden anxiety, followed
by shivering at his house. On taking him to a local hospital, he was declared “brought dead.” As per the history
furnished by the police, he was a known drug addict for
many years. External examination revealed multiple,
transverse, linear, parallel scars on the back of the left
forearm, measuring 4-5 cm in length. Stomach contained
partly digested orange-coloured rice and chicken meal,
with some blue coloured particles. The contents had an
unusual smell, and the gastric mucosa appeared congested. Chemical analysis revealed the presence of
dextropropoxyphene in the samples sent.
Introduction
Spasmo-Proxyvon® is a popular antispasmodic drug from
Wockhardt that is increasingly being abused of late.1 This
paper highlights three cases of death due to addiction to
Spasmo-Proxyvon®. Autopsies were conducted in the
Department of Forensic Medicine of Victoria, Bowring
& Lady Curzon Hospital, Bengaluru.
Case 3
A 45-year-old male was found dead at a bus-stand. History furnished by the police suggested he had been absconding from his home due to drug addiction for the
past few years. Some strips of Spasmo-Proxyvon® tablets were found in his trouser pockets. Autopsy revealed
bluish discolouration of the stomach mucosa, with un-
Dept. of Forensic Medicine & Toxicology, Bangalore Medical College & Research Institute, Bengaluru.
*
Author for correspondence: [email protected]
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JOURNAL OF THE INDIAN SOCIETY OF TOXICOLOGY (JIST)
usual smell of the contents. Intestinal mucosa showed
dark discolouration. Chemical analysis of blood and viscera samples revealed the presence of dextropropoxyphene.
In all three cases the cause of death was opined as “respiratory failure as a result of consumption of a substance
containing dextropropoxyphene”.
Discussion
Spasmo-Proxyvon® is one of the most commonly prescribed antispasmodic drugs in India, manufactured by
Wockhardt, and contains 2 acetaminophen (i.e.,
paracetamol 400 mg), dicyclomine hydrochloride (10 mg),
propoxyphene napsylate (100 mg), and permitted blue
dye in gelatin capsule form. It is a schedule ‘H’ drug,
and should not be sold without prescription. But in reality, it is easily available over the counter.3 SpasmoProxyvon® is indicated for the relief of spasmodic pains
due to renal colic, abdominal muscle cramps, irritable
bowel syndrome, etc.
Dextropropoxyphene is a synthetic opioid chemically dissimilar to morphine, but quite similar in analgesic action
and adverse effect profile to codeine, except that it is a
poor antitussive, and probably less constipating. It is primarily metabolized in the liver.4 It has a half-life of 6 to
12 hours. However, its metabolite, norpropoxyphene
(NPP) has a half-life of 30 to 36 hours. After oral ingestion, onset of effects is usually within 1 hour, with
peak plasma concentrations achieved within 2-2½ hours.
Repeated doses (at intervals of 6 hrs), lead to increasing
plasma concentrations, eventually reaching a plateau at/
after the 9th dose (about 48 hrs).5
In parts of Southern India, it was noted that the key ingredient in these preparations has changed from
dextropropoxyphene hydrochloride to dextropropoxyphene napsylate. There are some key differences between these formulations:
■ First, the napsylate salt form is water-insoluble. Hence,
it cannot be abused by the parenteral route (ie. by
injection).
■ Second, approximately 100 mg of dextropropoxyphene
napsylate is equivalent to 65 mg of dextropropoxyphene HCl.
■ Third, the onset of action of the napsylate salt is slightly
longer (about an hour) than that of the HCl salt.
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Normally the therapeutic concentration for dextropropoxyphene is about 0.4 mg/L, and plasma concentration
in serious toxicity is found to be over 1 mg/L5. Convulsions and delirium are the major effects of overdose.
Adverse effects on chronic use comprise impairment of
mental performance, drowsiness, lethargy, blurred vision,
miosis, decreased appetite, inhibition of the cough reflex
(antitussive effect), respiratory depression, and constipation.6
Dicyclomine (dicloverine) is a synthetic tertiary amine,
which is a muscarinic receptor antagonist. It has a direct, smooth muscle relaxant action, in addition to antispasmodic and antiemetic properties. Atropinic side effects are usually not present at antispasmodic doses. It
is commonly used for treating irritable bowel syndrome,
motion sickness, morning sickness, rectal urgency, abdominal cramps, dysmenorrhoea, etc.4 Overdose can
cause atropinic effects such as dry mouth, dilated pupils,
palpitations, psychotic behaviour, delirium, hallucinations,
CVS collapse and respiratory depression. It is contraindicated in people with narrow iridocorneal angle and prostatic hypertrophy. The normal therapeutic dose is 10-20
mg orally, three or four times a day.4
Acetaminophen (paracetamol) is a para-aminophenol
derivative, and is an analgesic- antipyretic with poor antiinflammatory action. It has a central analgesic action
(raising the pain threshold). Plasma half-life is about 2-3
hours, and effective oral dose lasts 3-5 hours. It is one of
the most commonly used over-the-counter analgesicantipyretic drugs, used in doses of 0.5-1 gm three times
a day. Adverse effects are rare, as the drug is well tolerated, but chronic use can cause analgesic nephropathy.
Acute poisoning can cause centrilobular hepatic necrosis, hypoglycaemia, etc. Fulminant hepatic failure and
death are likely if the plasma levels are above 200 mcg/
ml at 4 hrs, and 30 mcg/ml at 15 hrs of ingestion.7
The maximum doses for the constituents of SpasmoProxyvon® are as follows:
■ Acetaminophen: 2-4 grams/day
■ Dextropropoxyphene HCl: 390 mg/day
■ Dextropropoxyphene napsylate: 600 mg/day
■ Dicyclomine: No available safety data for doses above
80 mg/day.7
CASE REPORT: FATALITY FROM SPASMO-PROXYVON ADDICTION
Spasmo-Proxyvon® costs less than Rs.12 for each strip.
Just three tablets dissolved in soda water gives the user
the desired euphoria, which lasts for more than three
hours. The effect is said to be stronger when it is dissolved in soft drinks. Tolerance develops in the user over
a period of time, who ends up using the drug in higher
doses than usual, eventually leading to fatality. Sometimes the drug user dissolves the capsule in water and
injects it intravenously, not knowing that the napsylate
form of propoxyphene is water-insoluble and settles under the veins causing gangrene due to vascular compromise. Each “shot” is made from four to six capsules.
Unlike heroin, the effect of each shot lasts three minutes, making an addict take a dozen shots a day. As multiple shots into the same vein is painful, addicts use different veins, causing multiple abscesses in various parts,
over a period of time.
With the realization of these problems, the government
is in the process of implementing more stringent measures to prevent easy accessibility.8 However, it needs
to be seen whether these measures will bear fruit, and
the incidence of abuse along with associated problems
will come down in the future.
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REFERENCES
1. Ignatius Pereira. Rampant abuse of allopathic drugs. The Hindu,
Friday, June 18, 2004.
2. Spasmo-Proxyvon® [cap], Class - Antispasmodics. CIMS Beta
India. URL: http://www.cimsasia.com/Page.aspx?menuid =
mng&name = SPASMO-PROXYVON + cap&h = spasmo,
proxyvon & CTRY = IN & searchstring = spasmo + proxyvon.
3. Ambika Sharma. Schedule H drugs being sold without prescription. The Tribune, Wednesday, January 4, 2006.
4. Tripathi KD. Essentials of Medical Pharmacology. 5th edn, 2003.
Jaypee Brothers Medical Publishers, New Delhi. p426.
5. Dart RC. Medical Toxicology. 3rd edn, 2003. Lippincot Williams
& Wilkins, Philadelphia.
6. Miller RL. Propoxyphene. In: The Encyclopedia of Addictive
Drugs. 2002. Greenwood Press, London. 390-393.
7. Brunton L, Parker K, Blumentel D, Buxton L (editors). Goodman
& Gillman’s Manual of Pharmacology and Therapeutics. 11th
edn, 2008. McGraw Hill. 445.
8. Neha Dixit. Hacked by the needle. Tehelka Magazine, Vol 5,
Issue 14, April 12, 2008.