Between 9pm on Saturday and 6am on Sunday the westbound section of the contraflow will be closed to allow vital repairs to a pothole and sinking drain in the carriageway.
A clearly signposted diversionary route will be in place during the closure.
The eastbound lane of the contraflow is unaffected and remains open throughout.
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The repair work is being carried out by Network Rail on behalf of Highways England.
Network Rail workers are already on site reconstructing Higham Road Bridge, thereby ensuring it is dealt with efficiently and removes any risk to motorists.
A company statement said: ”Network Rail would like to apologise for any disruption caused by the closure and thank road users for their patience whilst these important repairs take place.
“The contraflow has been in place since February, when the main westbound carriageway of the A45 was closed to allow Higham Road Bridge to be demolished and rebuilt as part of the Midland Main Line Upgrade.
“The bridge is being raised to allow for the safe clearance of overhead line equipment in anticipation of electrification of the route between London to Kettering and Corby via Bedford.
“Work remains on schedule to allow the road to re-open on Wednesday, October 16.”