Murray S. Kessler
President and Chief Executive Officer at Perrigo
Thank you, Brad, and good morning, everyone. First and foremost, I'd like to start this call by acknowledging and thanking the Perrigo team, 10,000 strong. No matter what COVID-related adversity has been thrown their way over the last two years from lockdowns to multiple COVID variants to cough/cold impact to supply chain disruption, they kept our organization running, providing society with essential products. And they did so without having to shut down a single shift during the last two years in any one of our manufacturing facilities worldwide. Incredible.
I also want to take a moment to acknowledge our Ukrainian colleagues that are in the midst of the horrible unprovoked invasion by Russia. Our hearts and support are with you. They were part of the entire Perrigo team that helped us complete our transformation to a consumer self-care company in 2021 despite pandemic disruption by accomplishing our three largest strategic milestones.
First, selling the generic Rx business for $1.6 billion, which dramatically lowers volatility and places consumer self-care as our sole strategic focus. Two, redeploying the Rx sale proceeds by announcing our agreement to acquire HRA Pharma, a rapidly growing consumer self-care company with a portfolio of leading brands for EUR1.8 billion. We estimate HRA will add EUR400 million in revenue and EUR150 million in operating income in 2023. And three, favorably settling the EUR1.6 billion Irish Tax NoA that had been a significant overhang on the company since I joined three years ago.
This tax assessment could have cost the company $3 billion or more, including interest and penalties. We settled it for EUR266 million, and this issue is now completely resolved and behind us. And we paid for the settlement using the proceeds from a favorable EUR355 million arbitration award. As a side note, we have some late-breaking news on the $370 million interest rate deductibility in Notice of Proposed Assessment, the NOPA, we received from the IRS in May of 2020. After a number of discussions with the IRS, the tax assessment has been lowered from $370 million to $130 million. That doesn't mean it will end up being $130 million as we will continue to vigorously defend ourselves on the technical merits.
But it does mean the risk is dramatically reduced, and this is just another example of our determination and success clearing the decks of all major overhangs while protecting shareholder value. With these major achievements behind us, Perrigo is now a pure-play consumer self-care company poised for strong growth, unencumbered by major overhangs of the past. Furthermore, Perrigo has been returned to a company that is consistently growing its top line. In fact, our consumer businesses have grown 3% on a compound annual basis over the past three years despite the historically weak 2021 cough/cold season.
Remember, cough/cold related products represent nearly 20% of our total business. But for that, our CAGR would have been even stronger. But plus 3% is still solid growth especially compared to the prior three-year compound annual growth rate of minus 1%, prior to our transformation. While our big three strategic priorities were accomplished and we have returned to consistent top line growth, our original 2021 financial objectives were not met, although earnings did finish just above the midpoint of our revised guidance.
On a total year basis, adjusted EPS finished at $2.06, down 12% versus a year ago due to last year's historically weak cough/cold season and its impact on manufacturing productivity, along with severe material price inflation and supply chain disruption in the second half of the year. These factors, including the step down in margin due to sales to the divested Rx business, negatively impacted fourth quarter gross margin by roughly 400 basis points, which is basically the same as most leading CPG companies. I'm encouraged by our fourth quarter metrics and how we exited the year, however.
Fourth quarter net sales grew 5%, adjusted operating income increased 12%, and adjusted diluted EPS increased 28% versus a year ago as higher gross profit, new products and lower operating expenses overcame industry headwinds. Fourth quarter net sales growth was driven by: one, a return to strong cough/cold demand, evidenced by 28% growth in our Upper Respiratory reporting category, which also includes allergy; two, 12% growth in Nutrition behind share gains in U.S. infant formula and the successful launch of new products and oral electrolytes. In fact, one of our new adult electrolyte drinks won the Product of the Year
Award as voted on by one of the largest customers that we have. And it's a tremendous recognition for the efforts of the Perrigo team. And three, lastly, fourth quarter growth was also the result of strong contract tax sales, including sales to the divested Rx business. Also encouraging, as shown on Slide 10, Perrigo sales growth accelerated sequentially each quarter of 2021 as COVID-related disruptions either slowed or were addressed by the Perrigo team.
This positive trend has continued into January and February of this year. We entered 2022 with strong top line momentum and strong global consumer demand. The markets we compete in the U.S.A. were up in the fourth quarter 17.5% for OTC, 24.7% for Nutrition and plus 9.1% for Oral Care. And in Europe, demand for our essential products were plus 33% and plus 2% for our self-care products. We also entered 2022 with most major top line headwinds behind us.
Higher illnesses and the increased spread of the Omicron variant, which tends to cause traditional cold and flu-like symptoms, has contributed to a significant rebound in cough/cold sales. Customer inventories, which were a bit heavy in 2021 due to the weak cough/cold season, have been worked down to normal levels. And we have taken numerous supply chain and logistics corrective actions allowing us to ship our products, albeit at a higher cost. And I'm proud to say we entered 2022 with a robust offering of innovative new products as shown on Slide 13. For all of these reasons, we expect strong top line growth in our business in 2022.
And to be clear, that is before any additional net sales from the HRA acquisition. Worth mentioning, HRA sales and earnings growth was robust in 2021 and was in line with our expectations. While the top line should be strong year-over-year, gross margin pressure will continue to affect the first half of 2022. We expect gross margin pressure to ease in the second half of the year as we start to receive the financial benefit from normalized cough/cold sales, certain input costs started to ease, our pricing actions being fully implemented and the negative margin-only impact from the Rx divestiture annualizes. To be clear, we expect relatively flat gross margin in 2022, excluding HRA, with their second half stronger than the first.
Once the deal closes, HRA will be further accretive to our second half gross margin given it is a substantially higher gross margin than our products. All of this leads us to an adjusted EPS guidance range of $2.10 to $2.30 per share driven by organic net sales growth of an estimated 7% to 8%. Assuming the acquisition of HRA closes on June 30th, we expect it would add an additional $170 million to $190 million in net sales and approximately $0.30 of adjusted diluted EPS to our base Perrigo guidance.
Please note this guidance does not include any potential impact from the Russian invasion of Ukraine. Our 2022 guidance includes between $10 million and $15 million of operating income from these two countries, two months of which though have already been realized. But it's really too early to estimate the potential full year impact. And frankly, our top priority right now is on the safety of our colleagues and their families in the region.
Looking at the path ahead, we believe we are poised to create significant value, and it is clear what needs to be done to make that happen. First, continue to execute on the self-care strategy and continue to deliver organic growth, including recovery of cough/cold, strong digital growth and rapid innovation. Second, successfully close and integrate HRA, which will provide a step change increase in sales, income, margins and EPS. And third, stabilize and then aggressively grow gross margins through our global supply chain redesign project, which will occur concurrent with the HRA integration.
So in conclusion, we are excited about the opportunities over the next few years and beyond as the company is well positioned for success. At the same time, we are planning pragmatically given the challenges in the current environment. It remains our goal, however, to complete the job and deliver our original objectives from our investor conference three years ago.
With that, I'll turn the call over to Ray Silcock to discuss the financials in more details. Ray?