Attention of veterinarians is drawn to this information prescribing halofuginone (as a restricted veterinary medicine), and veterinarians selling EXAGEN and KRYPTADE as an over-the-counter in-feed medication.

Important information when using both halofuginone lactate and beta-cyclodextrin simultaneously. Both drugs have approved label claims for use as preventative aids to control or limit the effects of outbreaks from Cryptosporidium parvum in young calves. No advice is available of any potential benefits or adverse reactions when using the drugs at the same time.

However there is a likely potential drug interaction between EXAGEN, and halofuginone lactate (Halocur) when they are used prophylactically. This interaction may interfere with beta-cyclodextrin’s oocystocidal activity, limiting its ability to act as a preventative and treatment aid against the risk of cryptosporidiosis scours in young calves. Some potential for interaction exists between KRYPTADE and HALOCUR when treating calves therapeutically  for rehydration to improve their rate of recovery from calves with scours associated with cryptosporidiosis.

 “When calves are already receiving administration of halofuginone lactate (either Halocur and Halagon), it is possible that beta-cyclodextrin (in BOTH Kryptade and Exagen) given simultaneously may not provide the benefits expected from beta-cyclodextrin described on the label.”

“Once halofuginone lactate is stopped however e.g. at day 7 as indicated on the label, there may be additional benefits to then apply beta-cyclodextrin to limit the output of oocysts.”

Further:

Prophylaxis for Cryptosporidial infection and associated scours

Halofuginone lactate is a cryptosporidiostatic drug, halting but not killing the intermediate cryptosporidial life stages prior to the release of the oocysts. As beta-cyclodextrin only acts on the oocysts, the absence of oocysts while calves are being dosed with halofuginone lactate, means there are relatively low numbers or no oocysts present for beta-cyclodextrin to act upon. This constitutes a drug-to-drug interaction. It applies so long as the static effects of halofuginone lactate are present, and should be considered before using either Kryptade and/or Exagen.” Given that both products are recommended for use for the earliest stages of the calf’s life, some consideration should be given as to which product is most suitable.

If a calf is being treated with haluginone lactate and it subsequently develops diarrhoea, stop this treatment with Halocur. Signs of toxicity mimic scours due to Cryptosporidium parvum infections (see leaflet for Halocur). Treatment of calves with scours using halofuginone lactate are at particular risk of toxicity as a result of reduced renal perfusion. Care is also required that Halofuginone is not given on an empty stomach (administer 2 hours after feeding) It is a contra-indication on Halocur’s label with advice not to use it in scouring calves of more than 24 hours duration, and to then only use it with electrolytes. As dehydration of scours can occur before visible scouring actually occurs some calves may be at risk of reduced renal perfusion even when following the label instructions. This may particularly apply if halofuginone lactate treatment is started as a prophylactic in older calves.

Therapeutic treatment of calves with cryptosporidiosis requiring rehydration

Start treatment with Kryptade to ensure

  1. calves with cryptosporidiosis scours are rehydrating and having the benefit of the antioocystocidal action of beta-cyclodexin without the interaction from halofuginone lactate, and sick scouring calves are not exposed to additional risk factors that lead to signs of toxicity and possible death of calves
  2. calves are rehydrated and able to experience the earlier recovery from KRYPTADE and beta-cyclodextrin and the reduction of the period of electrolyte adminstration when scours are associated with cryptosporidiosis.

On the other hand when haloguginone is used a prohpylactic as recommended on the label for 7 days, the use of EXAGEN may be specifically indicated. Once Halocur is withdrawn the loss of inhibition of halofuginone produces a surge in oocyst output over the next 7-20 days. This leads to a massive resurgence of oocysts, and gross contamination of the calf shed. This potentially counterproductive if the goal is to reduce the environmental contamination of oocysts. In this instance the use of EXAGEN can maintain the low output pf oocyst if it is used immediately halufuginone lactate is withdrawn. This will limit output of oocysts and the opportunity that this may lead to cryptosporidial scours.

The use of EXAGEN from soon after birth is recommended for protection from scours associated with cryptosporidial infection. This may be given without the risk of toxic side reactions as reported and managed with stringent label restrictions seen with halofuginone lactate. EXAGEN administration is recommended to be given twice daily mixed in colostrum, transition colostrum and/or milk.. Clinical signs of scours if seen do not imclude the signs associated with cryptosporidiosis – notably the absence of loss of appetite, and depression. Scours and the risk of dehydration are easily managed with isotonic electrolyte solution (such as KRYPTADE or ENERVADE) even as ad lib fluids overnight.

References: pers comm B A Pauling