Tramadol Mixture

Tramadol is available in Australia in several commercial presentations:

• Immediate release capsules: 50mg
• Modified release tablets: 50mg, 100mg, 150mg, 200mg
• Oral drops: 100mg/mL
• Injection: 100 mg/2mL

It is a highly effective synthetic opioid analgesic for moderate to severe pain. It is useful for both nociceptive pain as well as some neuropathic pain, and is commonly introduced when non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol prove to be ineffective in maintaining pain relief.

Recommended doses for orally administered tramadol are as follows:

Adults

The maximum dose of 400mg/day should be divided according to the pharmacokinetic attributes of the formulations.

• Immediate release: 50mg – 100mg every four to six hours when necessary
• Controlled release: 50mg – 200mg every twelve hours
• Extended release: 100mg – 300mg daily

Paediatrics

While tramadol has not been registered for use in children, it is prescribed at the discretion of the medical practitioner for children above one year old, and is deemed appropriate by specialist children’s hospitals such as The Royal Children’s Hospital, who publish a fact sheet providing dose and administration guidelines.

• 1 – 2mg/kg every four hours when necessary (specialist advice recommended)
• Maximum dose of 400mg/day

Veterinary
The Merck Veterinary Manual provides dosage guidelines for analgesic use in dogs and cats.

• Cats: 1 – 4mg/kg every six to eight hours
• Dogs: 5 – 10mg/kg every six to eight hours

Tramadol is popular due to its ability to provide pain relief similar to that of morphine (where 50mg of oral tramadol is equivalent to 10mg of oral morphine), while having a lower risk of dependence and the associated diversion and abuse. Consequently, it is one of the very few opioid analgesics included in Schedule 4: Prescription only Medicine, or Prescription Animal Remedy of the standard for the Uniform Scheduling of Medicines and Poisons No. 3 (SUSMP). Recently, tramadol has also been used to provide relief for opioid withdrawal.

Adverse effects include: headache, nausea, dizziness, constipation, drowsiness, and difficulty concentrating.  It is also important that tramadol is not used in conjunction with any monoamine oxidase inhibitors (MAOIs),  antidepressants such as selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenergic reuptake inhibitors (SNRIs), or St John’s Wort in both human and animals, or in animals with a recent history of seizures. This is due to tramadol’s mode of action that facilitates the release of serotonin, and the risk of excess serotonin leading to serotonin syndrome.

Serotonin syndrome is a toxic state that can be life threatening with the following clinical features:

• Cognitive: Confusion, agitation, hypomania, hyperactivity, restlessness
• Autonomic: Hyperthermia, sweating, tachycardia, hypertension, mydriasis, flushing, shivering
• Neuromuscular: Clonus (spontaneous/inducible/ocular), hyperreflexia, hypertonia, ataxia, tremor

Symptoms of overdose for tramadol are similar to other opioid analgesics, which include respiratory depression, seizures, circulatory collapse and cardiac arrest.

Tramal^® Oral Drops, a commercial liquid formulation, offers dose flexibility in Australia, with a concentration of 100mg/mL of tramadol.

Table 1. Dosage Measurements for Tramal^® Oral Drops 100mg/mL

This product has raised safety concerns due to the risk of morbidity or mortality related to miscalculation or incorrect measurement.  Furthermore, lower doses become difficult to measure, such as 15mg (6 drops), which could result in overdose if more drops than required are accidentally released.

With these concerns, the Royal Children’s Hospital in Victoria, amongst others, has chosen not to use these drops within hospital, but instead recommended the use of tramadol capsules, with the contents being dispersed in 10mL of water to create a 5mg/mL mixture, before measuring out the nominated dose and administering to the patient.

HPS Compounding in South Australia has developed an alternative product to more closely meet the needs of clients, and now offer tramadol mixture at a concentration of 10mg/5mL (2mg/mL).  This concentration provides both doctors and veterinarians with the flexibility to tailor specific doses for their clients. With this formulation, dose miscalculations present a lower risk to the patient e.g. 10mL of HPS’ formulation delivers 20mg of tramadol, where 10mL of Tramal^® Drops delivers 1000mg, over double the recommended daily maximum for humans.

HPS Compounding is pleased to provide solutions for clients that can prevent sentinel events, and expect to offer other flexible product presentations where doses are based on mg/kg calculations. This includes for children, patients who have difficulty swallowing, patients who prefer liquid over solid forms or concentrated drops, or pets. HPS’s tramadol mixture may be used with more confidence.